uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446360080  12 VDIVNEENEVIAQASREQMRAQCLRHRATYIVVHDGMGKILVQRRTETKDFLPGMLDATAGGVVQADEQLLESARREAEE 91
Cdd:cd04697    1 VDIVDENNEVVGAATRAEMRRQKLIHRATYIVVRNAAGRLLVQKRTMDKDYCPGYLDPATGGVVGAGESYEENARRELEE 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 446360080  92 ELGIAGVPFAEHGQFYFEDKNCRVWGALFSCVSHGPFALQEDEVSEVCWLTPEEIT--ARCDEFTPDSLKALALWMK 166
Cdd:cd04697   81 ELGIDGVPLRPLFTFYYEDDRSRVWGALFECVYDGPLKLQPEEVAEVDWMSEDEILqaARGEEFTPDGRVALERYLA 157

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446360080   35 LRHRATYIVVHDGMGKILVQRRTetKDFLPGMLdATAGGVVQADEQLLESARREAEEELGIAG-----VPFAEHGQFY-F 108
Cdd:pfam00293   1 KRRVAVGVVLLNEKGRVLLVRRS--KKPFPGWW-SLPGGKVEPGETPEEAARRELEEETGLEPellelLGSLHYLAPFdG 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 446360080  109 EDKNCRVWGALFSCVSHGPFALQ-EDEVSEVCWLTPEEI 146
Cdd:pfam00293  78 RFPDEHEILYVFLAEVEGELEPDpDGEVEEVRWVPLEEL 116

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446360080  12 VDIVNEENEVIAQASREQMRAQCLRHRATYIVVHDGMGKILVQRRTETKDFLPGMLDATAGGVVQADEQLLESARREAEE 91
Cdd:cd04697    1 VDIVDENNEVVGAATRAEMRRQKLIHRATYIVVRNAAGRLLVQKRTMDKDYCPGYLDPATGGVVGAGESYEENARRELEE 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 446360080  92 ELGIAGVPFAEHGQFYFEDKNCRVWGALFSCVSHGPFALQEDEVSEVCWLTPEEIT--ARCDEFTPDSLKALALWMK 166
Cdd:cd04697   81 ELGIDGVPLRPLFTFYYEDDRSRVWGALFECVYDGPLKLQPEEVAEVDWMSEDEILqaARGEEFTPDGRVALERYLA 157

uncharacterized NUDIX hydrolase subfamily; NUDIX hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of NUDIX hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446360080  12 VDIVNEENEVIAQASREQMRAQCLRHRATYI-VVHDGMGKILVQRRTETKDFLPGMLDATAGGVVQADEQLLESARREAE 90
Cdd:cd04692    1 LDIVDEDGRPIGVATRSEVHRQGLWHRTVHVwLVNPEEGRLLLQKRSANKDDFPGLWDISAAGHIDAGETYEEAAVRELE 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 446360080  91 EELGIA---------GVPFAEHGQFYFEDkNCRVWgaLFSCVSHGP---FALQEDEVSEVCWLTP 143
Cdd:cd04692   81 EELGLTvspedliflGVIREEVIGGDFID-NEFVH--VYLYETDRPleeFKLQPEEVAGVVFVDL 142

Isopentenyl diphosphate isomerase; Isopentenyl diphosphate (IPP) isomerase, a member of the NUDIX hydrolase superfamily, is a key enzyme in the isoprenoid biosynthetic pathway. Isoprenoids comprise a large family of natural products including sterols, carotenoids, dolichols and prenylated proteins. These compounds are synthesized from two precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). IPP isomerase catalyzes the interconversion of IPP and DMAPP by a stereoselective antarafacial transposition of hydrogen. The enzyme requires one Mn2+ or Mg2+ ion in its active site to fold into an active conformation and also contains the NUDIX motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), that functions as a metal binding and catalytic site. The metal binding site is present within the active site and plays structural and catalytical roles. IPP isomerase is well represented in several bacteria, archaebacteria and eukaryotes, including fungi, mammals and plants. Despite sequence variations (mainly at the N-terminus), the core structure is highly conserved.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446360080  12 VDIVNEENEVIAQASREQM-RAQCLRHRATYIVVHDGMGKILVQRRTETKDFLPGMLDATAGGVVQADEQLLESARREAE 90
Cdd:cd02885    2 VILVDEDDNPIGTAEKLEAhRKGTLLHRAFSVFLFNSKGELLLQRRALSKYTWPGLWTNTCCSHPLPGEGVEDAAQRRLR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446360080  91 EELGIAGVPFAEHGQFYFEDKNCRVWG-----ALFSCVSHGPFALQEDEVSEVCWLTPEEI----TARCDEFTPdslkal 161
Cdd:cd02885   82 EELGIPVCDLEELPRFRYRATDDNGLVeheidHVFVGRADGDPVPNPEEVSDYRWVSLEELrellAATPEAFTP------ 155

                 ....*
gi 446360080 162 alWMK 166
Cdd:cd02885  156 --WFR 158

isopentenyl-diphosphate Delta-isomerase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446360080   7 ASTEWVDIVNEENEVIAQASREQM-RAQCLRHRATYIVVHDGMGKILVQRRTETKDFLPGMLDATAGGVVQADEQLLESA 85
Cdd:PRK03759   3 METELVVLLDEQGVPTGTAEKAAAhTADTPLHLAFSCYLFDADGRLLVTRRALSKKTWPGVWTNSCCGHPQPGESLEDAV 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446360080  86 RREAEEELGIAGVPFA-EHGQFYF---------EDKNCRVWGALFScvshGPFALQEDEVSEVCWLTPEEITARCD---- 151
Cdd:PRK03759  83 IRRCREELGVEITDLElVLPDFRYratdpngivENEVCPVFAARVT----SALQPNPDEVMDYQWVDPADLLRAVDatpw 158

                        170       180
                 ....*....|....*....|....*....
gi 446360080 152 EFTPdslkalalWMKRNAKNEAVETETAE 180
Cdd:PRK03759 159 AFSP--------WMVLQAANLEARELLLA 179

thiamine diphosphokinase Tnr3 from Schizosaccharomyces pombe and similar proteins; Tnr3 is a bifunctional enzyme composed of a C-terminal thiamine pyrophosphokinase domain, which transfers pyrophosphate from ATP to thiamine and an N-terminal NUDIX hydrolase domain that converts oxidized derivatives of thiamine diphosphate (oxothiamine and oxythiamine) to their respective monophosphates. Members of the NUDIX hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belong to this superfamily requires a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of NUDIX hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the NUDIX hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance _ "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 446360080  43 VVHDGMGKILVQRRTETKDFLPGMLDATAGGVVQADEQLL 82
Cdd:cd03676   15 VRDGDGLRLWVARRSATKATYPGKLDNLVAGGVPAGESPL 54