Rossmann-fold NAD(P)(+)-binding proteins; A large family of proteins that share a Rossmann-fold NAD(P)H/NAD(P)(+) binding (NADB) domain. The NADB domain is found in numerous dehydrogenases of metabolic pathways such as glycolysis, and many other redox enzymes. NAD binding involves numerous hydrogen-bonds and van der Waals contacts, in particular H-bonding of residues in a turn between the first strand and the subsequent helix of the Rossmann-fold topology. Characteristically, this turn exhibits a consensus binding pattern similar to GXGXXG, in which the first 2 glycines participate in NAD(P)-binding, and the third facilitates close packing of the helix to the beta-strand. Typically, proteins in this family contain a second domain in addition to the NADB domain, which is responsible for specifically binding a substrate and catalyzing a particular enzymatic reaction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPyAVPYHYYMDIEEM------------------------------- 163
Cdd:cd12156 142 KRVGIVGLGRIGRAIARRLEAFGMEIAYHGRRPKP-DVPYRYYASLLELaaesdvlvvacpggpatrhlvnaevlealgp 220

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 164 HGVIVNVALGAIIDEEEM--------------------SNVPKELFELDNVVFSPHCAFMTLEGLEELGKVVVGNIEAFF 223
Cdd:cd12156 221 DGVLVNVARGSVVDEAALiaalqegriagagldvfenePNVPAALLDLDNVVLTPHIASATVETRRAMGDLVLANLEAFF 300

                .
gi 15241769 224 S 224
Cdd:cd12156 301 A 301

Hydroxy(phenyl)pyruvate Reductase, D-isomer-specific 2-hydroxyacid-related dehydrogenase; Hydroxy(phenyl)pyruvate reductase (HPPR) catalyzes the NADP-dependent reduction of hydroxyphenylpyruvates, hydroxypyruvate, or pyruvate to its respective lactate. HPPR acts as a dimer and is related to D-isomer-specific 2-hydroxyacid dehydrogenases, a superfamily that includes groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-Adenosylhomocysteine Hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPyAVPYHYYMDIEEM------------------------------- 163
Cdd:cd12156 142 KRVGIVGLGRIGRAIARRLEAFGMEIAYHGRRPKP-DVPYRYYASLLELaaesdvlvvacpggpatrhlvnaevlealgp 220

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 164 HGVIVNVALGAIIDEEEM--------------------SNVPKELFELDNVVFSPHCAFMTLEGLEELGKVVVGNIEAFF 223
Cdd:cd12156 221 DGVLVNVARGSVVDEAALiaalqegriagagldvfenePNVPAALLDLDNVVLTPHIASATVETRRAMGDLVLANLEAFF 300

                .
gi 15241769 224 S 224
Cdd:cd12156 301 A 301

D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain; This domain is inserted into the catalytic domain, the large dehydrogenase and D-lactate dehydrogenase families in SCOP. N-terminal portion of which is represented by family pfam00389.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769   115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKP---YAVPYHYYMDIEEM---------------------------- 163
Cdd:pfam02826  37 KTVGIIGLGRIGRAVAKRLKAFGMKVIAYDRYPKPeeeEEELGARYVSLDELlaesdvvslhlpltpetrhlinaerlal 116

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15241769   164 ---HGVIVNVALGAIIDEEEM-----------------SNVP----KELFELDNVVFSPHCA 201
Cdd:pfam02826 117 mkpGAILINTARGGLVDEDALiaalksgriagaaldvfEPEPlpadHPLLDLPNVILTPHIA 178

Hydroxy(phenyl)pyruvate Reductase, D-isomer-specific 2-hydroxyacid-related dehydrogenase; Hydroxy(phenyl)pyruvate reductase (HPPR) catalyzes the NADP-dependent reduction of hydroxyphenylpyruvates, hydroxypyruvate, or pyruvate to its respective lactate. HPPR acts as a dimer and is related to D-isomer-specific 2-hydroxyacid dehydrogenases, a superfamily that includes groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-Adenosylhomocysteine Hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPyAVPYHYYMDIEEM------------------------------- 163
Cdd:cd12156 142 KRVGIVGLGRIGRAIARRLEAFGMEIAYHGRRPKP-DVPYRYYASLLELaaesdvlvvacpggpatrhlvnaevlealgp 220

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 164 HGVIVNVALGAIIDEEEM--------------------SNVPKELFELDNVVFSPHCAFMTLEGLEELGKVVVGNIEAFF 223
Cdd:cd12156 221 DGVLVNVARGSVVDEAALiaalqegriagagldvfenePNVPAALLDLDNVVLTPHIASATVETRRAMGDLVLANLEAFF 300

                .
gi 15241769 224 S 224
Cdd:cd12156 301 A 301

Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxy acid dehydrogenase family; Formate dehydrogenase, D-specific 2-hydroxy acid dehydrogenase, Phosphoglycerate Dehydrogenase, Lactate dehydrogenase, Thermostable Phosphite Dehydrogenase, and Hydroxy(phenyl)pyruvate reductase, among others, share a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. 2-hydroxyacid dehydrogenases are enzymes that catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. Formate dehydrogenase (FDH) catalyzes the NAD+-dependent oxidation of formate ion to carbon dioxide with the concomitant reduction of NAD+ to NADH. FDHs of this family contain no metal ions or prosthetic groups. Catalysis occurs though direct transfer of hydride ion to NAD+ without the stages of acid-base catalysis typically found in related dehydrogenases. FDHs are found in all methylotrophic microorganisms in energy production and in the stress responses of plants. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-Adenosylhomocysteine Hydrolase, among others. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPYAVPYHY--YMDIEEM----------------------------- 163
Cdd:cd05198 141 KTVGIVGLGRIGQRVAKRLQAFGMKVLYYDRTRKPEPEEDLGfrVVSLDELlaqsdvvvlhlpltpetrhlineeelalm 220

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 164 --HGVIVNVALGAIIDEE-------------------EMSNVPKE--LFELDNVVFSPHCAFMTLEGLEELGKVVVGNIE 220
Cdd:cd05198 221 kpGAVLVNTARGGLVDEDallralksgkiagaaldvfEPEPLPADhpLLELPNVILTPHIAGYTEEARERMAEIAVENLE 300

                ..
gi 15241769 221 AF 222
Cdd:cd05198 301 RF 302

D-Mandelate Dehydrogenase-like dehydrogenases; D-Mandelate dehydrogenase (D-ManDH), identified as an enzyme that interconverts benzoylformate and D-mandelate, is a D-2-hydroxyacid dehydrogenase family member that catalyzes the conversion of c3-branched 2-ketoacids. D-ManDH exhibits broad substrate specificities for 2-ketoacids with large hydrophobic side chains, particularly those with C3-branched side chains. 2-hydroxyacid dehydrogenases catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Glycerate dehydrogenase catalyzes the reaction (R)-glycerate + NAD+ to hydroxypyruvate + NADH + H+. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769  95 NQSASTSGYDDPdlnqyqSKKRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPYAVPYH---YYMDIEEM-------- 163
Cdd:cd12168 141 RGFLDLTLAHDP------RGKTLGILGLGGIGKAIARKAAAFGMKIIYHNRSRLPEELEKAlatYYVSLDELlaqsdvvs 214

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 164 ---------HG--------------VIVNVALGAIIDEEEMS--------------------NVPKELFELDNVVFSPHC 200
Cdd:cd12168 215 lncpltaatRHlinkkefakmkdgvIIVNTARGAVIDEDALVdalesgkvasagldvfenepEVNPGLLKMPNVTLLPHM 294

                       170       180
                ....*....|....*....|....
gi 15241769 201 AFMTLEGLEELGKVVVGNIEAFFS 224
Cdd:cd12168 295 GTLTVETQEKMEELVLENIEAFLE 318

Putative D-isomer specific 2-hydroxyacid dehydrogenases, NAD-binding and catalytic domains; 2-Hydroxyacid dehydrogenases catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPYA-------------------------VPY----HYYMDIEEMH- 164
Cdd:cd12178 145 KTLGIIGMGRIGQAVARRAKAFGMKILYYNRHRLSEEtekelgatyvdldellkesdfvslhAPYtpetHHLIDAAAFKl 224

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 165 ----GVIVNVALGAIIDE--------------------EEMSNVPKELFELDNVVFSPHCAFMTLEGLEELGKVVVGNIE 220
Cdd:cd12178 225 mkptAYLINAARGPLVDEkalvdalktgeiagaaldvfEFEPEVSPELKKLDNVILTPHIGNATVEARDAMAKEAADNII 304

                       170
                ....*....|..
gi 15241769 221 AFFSNKPLLTPV 232
Cdd:cd12178 305 SFLEGKRPKNIV 316

Putative D-isomer specific 2-hydroxyacid dehydrogenases; 2-Hydroxyacid dehydrogenases catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKP--YAVPYHYYMDIEE-----------------------------M 163
Cdd:cd12165 138 KTVGILGYGHIGREIARLLKAFGMRVIGVSRSPKEdeGADFVGTLSDLDEaleqadvvvvalpltkqtrgligaaelaaM 217

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 164 --HGVIVNVALGAIIDEEEMSNVPKE---------------------------LFELDNVVFSPHCAFMTLEGLEELGKV 214
Cdd:cd12165 218 kpGAILVNVGRGPVVDEEALYEALKErpiagaaidvwwrypsrgdpvapsrypFHELPNVIMSPHNAGWTEETFRRRIDE 297

                       170
                ....*....|....*
gi 15241769 215 VVGNIEAFFSNKPLL 229
Cdd:cd12165 298 AAENIRRYLRGEPLL 312

Putative D-3-Phosphoglycerate Dehydrogenases, NAD-binding and catalytic domains; Phosphoglycerate dehydrogenases (PGDHs) catalyze the initial step in the biosynthesis of L-serine from D-3-phosphoglycerate. PGDHs come in 3 distinct structural forms, with this first group being related to 2-hydroxy acid dehydrogenases, sharing structural similarity to formate and glycerate dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily, which also include groups such as L-alanine dehydrogenase and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. Many, not all, members of this family are dimeric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKP-YAVPYHY-YMDIEE---------MH------------------- 164
Cdd:cd12172 143 KTLGIIGLGRIGKAVARRLSGFGMKVLAYDPYPDEeFAKEHGVeFVSLEEllkesdfisLHlpltpetrhlinaaelalm 222

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15241769 165 ---GVIVNVALGAIIDEEEMSN---------------------VPKELFELDNVVFSPHCAFMTLEGLEELGKVVVGNI 219
Cdd:cd12172 223 kpgAILINTARGGLVDEEALYEalksgriagaaldvfeeepppADSPLLELPNVILTPHIGASTKEAVLRMGTMAAQNV 301

glyoxylate reductase; Reviewed

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769  115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKP------------------------YAVPYH---YYMDIEEM---- 163
Cdd:PRK13243 151 KTIGIIGFGRIGQAVARRAKGFGMRILYYSRTRKPeaekelgaeyrpleellresdfvsLHVPLTketYHMINEERlklm 230

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769  164 --HGVIVNVALGAIIDEEEMSNVPKE--------------------LFELDNVVFSPHCAFMTLEGLEELGKVVVGNIEA 221
Cdd:PRK13243 231 kpTAILVNTARGKVVDTKALVKALKEgwiagagldvfeeepyyneeLFSLKNVVLAPHIGSATFEAREGMAELVAENLIA 310

                 .
gi 15241769  222 F 222
Cdd:PRK13243 311 F 311

Phosphoglycerate dehydrogenase (PGDH) NAD-binding and catalytic domains; Phosphoglycerate dehydrogenase (PGDH) catalyzes the initial step in the biosynthesis of L-serine from D-3-phosphoglycerate. PGDH comes in 3 distinct structural forms, with this first group being related to 2-hydroxy acid dehydrogenases, sharing structural similarity to formate and glycerate dehydrogenases. PGDH in E. coli and Mycobacterium tuberculosis form tetramers, with subunits containing a Rossmann-fold NAD binding domain. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-Adenosylhomocysteine Hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPYA------------------------VPYH---YYM----DIEEM 163
Cdd:cd05303 140 KTLGIIGFGRIGREVAKIARALGMNVIAYDPYPKDEQavelgvktvsleellknsdfislhVPLTpetKHMinkkELELM 219

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 164 H--GVIVNVALGAIIDE--------------------EEMSNVPKELFELDNVVFSPHCAFMTLEGLEELGKVVVGNIEA 221
Cdd:cd05303 220 KdgAIIINTSRGGVIDEeallealksgklagaaldvfENEPPPGSKLLELPNVSLTPHIGASTKEAQERIGEELANKIIE 299

                ..
gi 15241769 222 FF 223
Cdd:cd05303 300 FL 301

Putative D-isomer specific 2-hydroxyacid dehydrogenase; 2-Hydroxyacid dehydrogenases catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomains but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric. Formate dehydrogenase (FDH) catalyzes the NAD+-dependent oxidation of formate ion to carbon dioxide with the concomitant reduction of NAD+ to NADH. FDHs of this family contain no metal ions or prosthetic groups. Catalysis occurs though direct transfer of the hydride ion to NAD+ without the stages of acid-base catalysis typically found in related dehydrogenases. FDHs are found in all methylotrophic microorganisms in energy production and in the stress responses of plants.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPYAVPYHYYMDIEEMHGVI--------------------------- 167
Cdd:cd05300 135 KTVLIVGLGDIGREIARRAKAFGMRVIGVRRSGRPAPPVVDEVYTPDELDELLpeadyvvnalpltpetrglfnaerfaa 214

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 168 -------VNVALGAIIDEEEMSNV-------------------PKE--LFELDNVVFSPHCAFMTLEGLEELGKVVVGNI 219
Cdd:cd05300 215 mkpgavlINVGRGSVVDEDALIEAlesgriagaaldvfeeeplPADspLWDLPNVIITPHISGDSPSYPERVVEIFLENL 294

                       170
                ....*....|....
gi 15241769 220 EAFFSNKPLLTPVL 233
Cdd:cd05300 295 RRYLAGEPLLNVVD 308

C-terminal binding protein (CtBP), D-isomer-specific 2-hydroxyacid dehydrogenases related repressor; The transcriptional corepressor CtBP is a dehydrogenase with sequence and structural similarity to the d2-hydroxyacid dehydrogenase family. CtBP was initially identified as a protein that bound the PXDLS sequence at the adenovirus E1A C terminus, causing the loss of CR-1-mediated transactivation. CtBP binds NAD(H) within a deep cleft, undergoes a conformational change upon NAD binding, and has NAD-dependent dehydrogenase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 117 IGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPYAVPYHYY--MDIEE---------MH--------------------- 164
Cdd:cd05299 145 LGLVGFGRIGRAVAKRAKAFGFRVIAYDPYVPDGVAALGGVrvVSLDEllarsdvvsLHcpltpetrhlidaealalmkp 224

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 165 -GVIVNVALGAIIDE---------------------EEMSNVPKELFELDNVVFSPHCAFMTLEGLEELGKVVVGNIEAF 222
Cdd:cd05299 225 gAFLVNTARGGLVDEaalaralksgriagaaldvleEEPPPADSPLLSAPNVILTPHAAWYSEESLAELRRKAAEEVVRV 304

                ....*.
gi 15241769 223 FSNKPL 228
Cdd:cd05299 305 LRGEPP 310

D-2-hydroxyacid dehydrogenase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769   36 TGVDNQDLKS----NIVVVEVSPSPTlaqaslkmsqilPSVYLSTFSVASLLPVVLVLLDYFVN-----QSASTSGYDDP 106
Cdd:PRK08410  72 TGTNNVDIEYakkkGIAVKNVAGYST------------ESVAQHTFAMLLSLLGRINYYDRYVKsgeysESPIFTHISRP 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769  107 --DLNqyqsKKRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPYAVPYHYY--------MDIEEMH------------ 164
Cdd:PRK08410 140 lgEIK----GKKWGIIGLGTIGKRVAKIAQAFGAKVVYYSTSGKNKNEEYERVsleellktSDIISIHaplnektknlia 215

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769  165 ----------GVIVNVALGAIIDEEEMSNV-------------PKELFELDN----------VVFSPHCAFMTLEGLEEL 211
Cdd:PRK08410 216 ykelkllkdgAILINVGRGGIVNEKDLAKAldekdiyagldvlEKEPMEKNHpllsiknkekLLITPHIAWASKEARKTL 295

                        250
                 ....*....|....*
gi 15241769  212 GKVVVGNIEAFFSNK 226
Cdd:PRK08410 296 IEKVKENIKDFLEGG 310

Putative D-isomer specific 2-hydroxyacid dehydrogenases; 2-Hydroxyacid dehydrogenases catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 113 SKKRIGIVGLGSIGSKVATRLKAFGCQISYSSrnrkPYAVPYHYYMDIEE---------------MH------------- 164
Cdd:cd12171 146 RGKTVGIVGFGAIGRRVAKRLKAFGAEVLVYD----PYVDPEKIEADGVKkvsleellkrsdvvsLHarltpetrgmiga 221

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 165 ---------GVIVNVALGAIIDEEEMSNV--------------PKE-------LFELDNVVFSPHCAFMTLEGLEELGKV 214
Cdd:cd12171 222 eefalmkptAYFINTARAGLVDEDALIEAleegkiggaaldvfPEEplpadhpLLKLDNVTLTPHIAGATRDVAERSPEI 301

                ....*....
gi 15241769 215 VVGNIEAFF 223
Cdd:cd12171 302 IAEELKRYL 310

Putative D-3-Phosphoglycerate Dehydrogenases, NAD-binding and catalytic domains; Phosphoglycerate dehydrogenases (PGDHs) catalyze the initial step in the biosynthesis of L-serine from D-3-phosphoglycerate. PGDHs come in 3 distinct structural forms, with this first group being related to 2-hydroxy acid dehydrogenases, sharing structural similarity to formate and glycerate dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily, which also include groups such as L-alanine dehydrogenase and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. Many, not all, members of this family are dimeric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQ-ISYS---SRNRK-------PYA----------------VPYhyymdIEEMHGVI 167
Cdd:cd12174 136 KTLGVIGLGNIGRLVANAALALGMKvIGYDpylSVEAAwklsvevQRVtsleellatadyitlhVPL-----TDETRGLI 210

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 168 --------------VNVALGAIIDEEEMSNV---------------PKELFELDNVVFSPHCAFMTLEGLEELGKVVVGN 218
Cdd:cd12174 211 naellakmkpgailLNFARGEIVDEEALLEAldegklggyvtdfpePALLGHLPNVIATPHLGASTEEAEENCAVMAARQ 290

                ....*..
gi 15241769 219 IEAFFSN 225
Cdd:cd12174 291 IMDFLET 297

Phosphoglycerate Dehydrogenase, 2-hydroxyacid dehydrogenase family; Phosphoglycerate Dehydrogenase (PGDH) catalyzes the NAD-dependent conversion of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the first step in serine biosynthesis. Over-expression of PGDH has been implicated as supporting proliferation of certain breast cancers, while PGDH deficiency is linked to defects in mammalian central nervous system development. PGDH is a member of the 2-hydroxyacid dehydrogenase family, enzymes that catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-Adenosylhomocysteine Hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann-fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQI---------------SYSSRNRKPY---------AVPY----HYYMD---IEEM 163
Cdd:cd12155 136 KTILFLGTGSIGQEIAKRLKAFGMKVigvntsgrdveyfdkCYPLEELDEVlkeadivvnVLPLteetHHLFDeafFEQM 215

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 164 --HGVIVNVALGAIIDE----EEMSN---------------VPKE--LFELDNVVFSPHCAFMTLEGLEELGKVVVGNIE 220
Cdd:cd12155 216 kkGALFINVGRGPSVDEdaliEALKNkqirgaaldvfeeepLPKDspLWDLDNVLITPHISGVSEHFNERLFDIFYENLK 295

                       170
                ....*....|
gi 15241769 221 AFFSNKPLLT 230
Cdd:cd12155 296 SFLEDGELLK 305

Putative D-3-Phosphoglycerate Dehydrogenases; Phosphoglycerate dehydrogenases (PGDHs) catalyze the initial step in the biosynthesis of L-serine from D-3-phosphoglycerate. PGDHs come in 3 distinct structural forms, with this first group being related to 2-hydroxy acid dehydrogenases, sharing structural similarity to formate and glycerate dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily, which also include groups such as L-alanine dehydrogenase and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. Many, not all, members of this family are dimeric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKP---YAVPYHYYMDIEE---------MH--------GVI------- 167
Cdd:cd12169 143 KTLGIVGLGRIGARVARIGQAFGMRVIAWSSNLTAeraAAAGVEAAVSKEElfatsdvvsLHlvlsdrtrGLVgaedlal 222

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 168 -------VNVALGAIIDEEEMSN---------------------VPKELFELDNVVFSPHCAFMTLEGLEELGKVVVGNI 219
Cdd:cd12169 223 mkptallVNTSRGPLVDEGALLAalragriagaaldvfdveplpADHPLRGLPNVLLTPHIGYVTEEAYEGFYGQAVENI 302

                ....*.
gi 15241769 220 EAFFSN 225
Cdd:cd12169 303 AAWLAG 308

D-Lactate and related Dehydrogenases, NAD-binding and catalytic domains; D-Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate, and is a member of the 2-hydroxyacid dehydrogenase family. LDH is homologous to D-2-Hydroxyisocaproic acid dehydrogenase (D-HicDH) and shares the 2 domain structure of formate dehydrogenase. D-HicDH is a NAD-dependent member of the hydroxycarboxylate dehydrogenase family, and shares the Rossmann fold typical of many NAD binding proteins. D-HicDH from Lactobacillus casei forms a monomer and catalyzes the reaction R-CO-COO(-) + NADH + H+ to R-COH-COO(-) + NAD+. Similar to the structurally distinct L-HicDH, D-HicDH exhibits low side-chain R specificity, accepting a wide range of 2-oxocarboxylic acid side chains. (R)-2-hydroxyglutarate dehydrogenase (HGDH) catalyzes the NAD-dependent reduction of 2-oxoglutarate to (R)-2-hydroxyglutarate. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769  36 TGVDNQDL----KSNIVVVEVSPSPTLAQASLKMSQILpsvylstfsvaSLLPVVLVLLDYFVNQSASTSGYDDPDLNQy 111
Cdd:cd01619  76 TGYDNIDLdyakELGIGVTNVPEYSPNAVAEHTIALIL-----------ALLRNRKYIDERDKNQDLQDAGVIGRELED- 143

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 112 qskKRIGIVGLGSIGSKVATRLKAFGCQ-ISYS-SRNRKPYAVPYhYYMDIEE---------MH---------------- 164
Cdd:cd01619 144 ---QTVGVVGTGKIGRAVAQRAKGFGMKvIAYDpFRNPELEDKGV-KYVSLEElfknsdiisLHvpltpenhhmineeaf 219

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 165 -----GVI-VNVALGAIIDEE------------------------------EMSNVPKELFEL----DNVVFSPHCAFMT 204
Cdd:cd01619 220 klmkkGVIiINTARGSLVDTEaliealdsgkifgagldvledetpdllkdlEGEIFKDALNALlgrrPNVIITPHTAFYT 299

                       250
                ....*....|....*...
gi 15241769 205 LEGLEELGKVVVGNIEAF 222
Cdd:cd01619 300 DDALKNMVEISCENIVDF 317

Putative glycerate dehydrogenase and related proteins of the D-specific 2-hydroxy dehydrogenase family; This group contains a variety of proteins variously identified as glycerate dehydrogenase (GDH, also known as hydroxypyruvate reductase) and other enzymes of the 2-hydroxyacid dehydrogenase family. GDH catalyzes the reversible reaction of (R)-glycerate + NAD+ to hydroxypyruvate + NADH + H+. 2-hydroxyacid dehydrogenases catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann-fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 116 RIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKPYAvpyhyymDIEEMHG------------------------------ 165
Cdd:cd12164 134 RVGVLGLGELGAAVARRLAALGFPVSGWSRSPKDIE-------GVTCFHGeegldaflaqtdilvcllpltpetrgilna 206

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 166 ----------VIVNVALGAIIDEE---------EMSNV----------PKE--LFELDNVVFSPHCAFMTLegLEELGKV 214
Cdd:cd12164 207 ellarlprgaALINVGRGPHLVEAdllaaldsgHLSGAvldvfeqeplPADhpLWRHPRVTVTPHIAAITD--PDSAAAQ 284

                       170
                ....*....|....*
gi 15241769 215 VVGNIEAFFSNKPLL 229
Cdd:cd12164 285 VAENIRRLEAGEPLP 299

D-Erythronate-4-Phosphate Dehydrogenase NAD-binding and catalytic domains; D-Erythronate-4-phosphate Dehydrogenase (E. coli gene PdxB), a D-specific 2-hydroxyacid dehydrogenase family member, catalyzes the NAD-dependent oxidation of erythronate-4-phosphate, which is followed by transamination to form 4-hydroxy-L-threonine-4-phosphate within the de novo biosynthesis pathway of vitamin B6. D-Erythronate-4-phosphate dehydrogenase has the common architecture shared with D-isomer specific 2-hydroxyacid dehydrogenases but contains an additional C-terminal dimerization domain in addition to an NAD-binding domain and the "lid" domain. The lid domain corresponds to the catalytic domain of phosphoglycerate dehydrogenase and other proteins of the D-isomer specific 2-hydroxyacid dehydrogenase family, which include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence.

                        10        20
                ....*....|....*....|....*.
gi 15241769 114 KKRIGIVGLGSIGSKVATRLKAFGCQ 139
Cdd:cd12158 115 GKTVGIVGVGNVGSRLARRLEALGMN 140

Putative D-isomer specific 2-hydroxyacid dehydrogenases; 2-Hydroxyacid dehydrogenases catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQ-ISYSSRNRKP--------YAVP-------------YH----------------- 155
Cdd:cd12163 134 KRVGILGYGSIGRQTARLAQALGMEvYAYTRSPRPTpesrkddgYIVPgtgdpdgsipsawFSgtdkaslheflrqdldl 213

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 156 ------------YYMDIEEM------HGVIVNVALGAIIDEEEMSNV-------------------PK--ELFELDNVVF 196
Cdd:cd12163 214 lvvslpltpatkHLLGAEEFeilakrKTFVSNIARGSLVDTDALVAAlesgqirgaaldvtdpeplPAdhPLWSAPNVII 293

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 15241769 197 SPHCAFMTLEGLEELGKVVVGNIEAFFSNKPLLTPV 232
Cdd:cd12163 294 TPHVSWQTQEYFDRALDVLEENLERLRKGEPLINLV 329

Putative D-isomer specific 2-hydroxyacid dehydrogenases; 2-Hydroxyacid dehydrogenases catalyze the conversion of a wide variety of D-2-hydroxy acids to their corresponding keto acids. The general mechanism is (R)-lactate + acceptor to pyruvate + reduced acceptor. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxyacid dehydrogenase superfamily include groups such as formate dehydrogenase, glycerate dehydrogenase, L-alanine dehydrogenase, and S-adenosylhomocysteine hydrolase. Despite often low sequence identity, these proteins typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann fold NAD+ binding form. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 115 KRIGIVGLGSIGSKVATRLKAFGCQISYSSRNRKP----YAV-------PYHyymDI--------EEMHGVI-------- 167
Cdd:cd12166 133 RRVLIVGYGSIGRAIERRLAPFEVRVTRVARTARPgeqvHGIdelpallPEA---DVvvlivpltDETRGLVdaeflarm 209

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15241769 168 ------VNVALGAIIDEEEM------------SNV------PKE--LFELDNVVFSPHCAFMTLEGLEELGKVVVGNIEA 221
Cdd:cd12166 210 pdgallVNVARGPVVDTDALvaelasgrlraaLDVtdpeplPPGhpLWSAPGVLITPHVGGATPAFLPRAYALVRRQLRR 289

                ....*...
gi 15241769 222 FFSNKPLL 229
Cdd:cd12166 290 YAAGEPLE 297