TrkA-N domain; This domain is found in a wide variety of proteins. These proteins include potassium channels, phosphoesterases, and various other transporters. This domain binds to NAD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489081130    9 VLGLGIFGRTVARELSNfDQDVIAIDIRESHVKEVADLVTKAAVGDITDKEFLLAVGIEHCDTVVIASGNNlESSVLAVM 88
Cdd:pfam02254   3 IIGYGRVGRSLAEELSE-GGDVVVIDKDEERVEELREEGVPVVVGDATDEEVLEEAGIEEADAVIAATGDD-EANILIVL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 489081130   89 HCKKL-GVPTIIAKAKNKIFEEVLYGIGATKVITP 122
Cdd:pfam02254  81 LARELnPDKKIIARANDPEHAELLRRLGADHVISP 115

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 489081130   1 MLKRKTVGVLGLGIFGRTVARELSNFDQDVIAIDIREShvkevADLVTKAAVGDITDKEFLLAVgiehCDTVVIA 75
Cdd:cd12175  139 ELSGKTVGIVGLGNIGRAVARRLRGFGVEVIYYDRFRD-----PEAEEKDLGVRYVELDELLAE----SDVVSLH 204

TrkA-N domain; This domain is found in a wide variety of proteins. These proteins include potassium channels, phosphoesterases, and various other transporters. This domain binds to NAD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489081130    9 VLGLGIFGRTVARELSNfDQDVIAIDIRESHVKEVADLVTKAAVGDITDKEFLLAVGIEHCDTVVIASGNNlESSVLAVM 88
Cdd:pfam02254   3 IIGYGRVGRSLAEELSE-GGDVVVIDKDEERVEELREEGVPVVVGDATDEEVLEEAGIEEADAVIAATGDD-EANILIVL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 489081130   89 HCKKL-GVPTIIAKAKNKIFEEVLYGIGATKVITP 122
Cdd:pfam02254  81 LARELnPDKKIIARANDPEHAELLRRLGADHVISP 115

Trk system potassium transporter TrkA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489081130   3 KRKTVGVLGLGIFGRTVARELSNFDQDVIAIDIRESHVKEVADLVTKAAV--GDITDKEFLLAVGIEHCDTVVIASGN-- 78
Cdd:PRK09496 230 PVKRVMIVGGGNIGYYLAKLLEKEGYSVKLIERDPERAEELAEELPNTLVlhGDGTDQELLEEEGIDEADAFIALTNDde 309

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489081130  79 -NLESSVLAvmhcKKLGVPTIIAKAKNKIFEEVLYGIGATKVITPeRDSgkrVASNLLR----RHIESIIYLEHG-ISMI 152
Cdd:PRK09496 310 aNILSSLLA----KRLGAKKVIALVNRPAYVDLVEGLGIDIAISP-RQA---TASEILRhvrrGDIVAVHSLRRGaAEAI 381

                        170
                 ....*....|....*....
gi 489081130 153 EFVIPKSWE--GQSLSELD 169
Cdd:PRK09496 382 EAVAHETSKvvGKPLKDLK 400

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 489081130   1 MLKRKTVGVLGLGIFGRTVARELSNFDQDVIAIDIREShvkevADLVTKAAVGDITDKEFLLAVgiehCDTVVIA 75
Cdd:cd12175  139 ELSGKTVGIVGLGNIGRAVARRLRGFGVEVIYYDRFRD-----PEAEEKDLGVRYVELDELLAE----SDVVSLH 204

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
                 ....*....|....*....|....*....|....*
gi 489081130   2 LKRKTVGVLGLGIFGRTVARELSNFDQDVIAIDIR 36
Cdd:cd12172  140 LYGKTLGIIGLGRIGKAVARRLSGFGMKVLAYDPY 174

Nucleoside-diphosphate-sugar epimerase [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489081130  16 GRTVARELSNFDQDVIAIDIRESHVKEVADLVT-KAAVGDITDKEFLLAVgIEHCDTVV----IASG----------NNL 80
Cdd:COG0451   12 GSHLARRLLARGHEVVGLDRSPPGAANLAALPGvEFVRGDLRDPEALAAA-LAGVDAVVhlaaPAGVgeedpdetleVNV 90

                         90
                 ....*....|....*....
gi 489081130  81 ESSVLAVMHCKKLGVPTII 99
Cdd:COG0451   91 EGTLNLLEAARAAGVKRFV 109

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
                 ....*....|....*....|....*....|....
gi 489081130   1 MLKRKTVGVLGLGIFGRTVARELSNFDQDVIAID 34
Cdd:cd12171  144 ELRGKTVGIVGFGAIGRRVAKRLKAFGAEVLVYD 177

NAD(P) binding domain of leucine dehydrogenase, phenylalanine dehydrogenase, and valine dehydrogenase; Amino acid dehydrogenase (DH) is a widely distributed family of enzymes that catalyzes the oxidative deamination of an amino acid to its keto acid and ammonia with concomitant reduction of NADP+. For example, leucine DH catalyzes the reversible oxidative deamination of L-leucine and several other straight or branched chain amino acids to the corresponding 2-oxoacid derivative. Amino acid DH -like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 489081130   2 LKRKTVGVLGLGIFGRTVARELSNFDQDVIAIDIRESHVKEVADL--VTKAAVGDITDKE 59
Cdd:cd01075   26 LEGKTVAVQGLGKVGYKLAEHLLEEGAKLIVADINEEAVARAAELfgATVVAPEEIYSVD 85

D-Lactate and related Dehydrogenase like proteins, 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-2-hydroxyisocaproate dehydrogenase-like (HicDH) proteins are NAD-dependent members of the hydroxycarboxylate dehydrogenase family, and share the Rossmann fold typical of many NAD binding proteins. HicDH from Lactobacillus casei forms a monomer and catalyzes the reaction R-CO-COO(-) + NADH + H+ to R-COH-COO(-) + NAD+. D-HicDH, like the structurally distinct L-HicDH, exhibits low side-chain R specificity, accepting a wide range of 2-oxocarboxylic acid side chains. 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
                 ....*....|....*....|....*....|....*
gi 489081130   2 LKRKTVGVLGLGIFGRTVARELSNFDQDVIAIDIR 36
Cdd:cd12187  137 LAGKTLGVVGTGRIGRRVARIARGFGMKVLAYDVV 171

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 489081130   1 MLKRKTVGVLGLGIFGRTVARELSNFDQDVIA------------IDIRESHVKEVADLVTKA 50
Cdd:cd12174  132 ELRGKTLGVIGLGNIGRLVANAALALGMKVIGydpylsveaawkLSVEVQRVTSLEELLATA 193