putative NUDIX hydrolase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  12 QLTNIPSYPVSSP--QAAVLVLISRGDNPSILFTKRAAHLRHHPGEVCFPGGMWEPGDDNLLVTAQREVHEEIGLPAGHI 89
Cdd:PRK10707   16 QLQRPQPNRETLNqrQAAVLIPIVRRPQPTLLLTQRSIHLRKHAGQVAFPGGAVDPTDASLIATALREAQEEVAIPPSAV 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  90 QLLGALPQSHTRAGTAVTPFVAHFDASINLQPSPDELESIFMVPLA-AFQAGLQVREDhFERHGHILRVPVYHYQGYEIW 168
Cdd:PRK10707   96 EVIGVLPPVDSSTGYQVTPVVGIIPPDLPYRANEDEVAAVFEMPLAeALHLGRYHPLD-IYRRGQSHRVWLSWYEQYFVW 174

                         170
                  ....*....|
gi 1150411341 169 GFTAAVTAQL 178
Cdd:PRK10707  175 GMTAGIIREL 184

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  24 PQAAVLVLISRGDNpSILFTKRAahLRHHPGEVCFPGGMWEPGDDnLLVTAQREVHEEIGLPAGHIQLLGALPQSHT--- 100
Cdd:pfam00293   2 RRVAVGVVLLNEKG-RVLLVRRS--KKPFPGWWSLPGGKVEPGET-PEEAARRELEEETGLEPELLELLGSLHYLAPfdg 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1150411341 101 --RAGTAVTPFVAHFDASINLQPSPDELESIFMVPLAAFQaglqvREDHFERHGHILR 156
Cdd:pfam00293  78 rfPDEHEILYVFLAEVEGELEPDPDGEVEEVRWVPLEELL-----LLKLAPGDRKLLP 130

putative NUDIX hydrolase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  12 QLTNIPSYPVSSP--QAAVLVLISRGDNPSILFTKRAAHLRHHPGEVCFPGGMWEPGDDNLLVTAQREVHEEIGLPAGHI 89
Cdd:PRK10707   16 QLQRPQPNRETLNqrQAAVLIPIVRRPQPTLLLTQRSIHLRKHAGQVAFPGGAVDPTDASLIATALREAQEEVAIPPSAV 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  90 QLLGALPQSHTRAGTAVTPFVAHFDASINLQPSPDELESIFMVPLA-AFQAGLQVREDhFERHGHILRVPVYHYQGYEIW 168
Cdd:PRK10707   96 EVIGVLPPVDSSTGYQVTPVVGIIPPDLPYRANEDEVAAVFEMPLAeALHLGRYHPLD-IYRRGQSHRVWLSWYEQYFVW 174

                         170
                  ....*....|
gi 1150411341 169 GFTAAVTAQL 178
Cdd:PRK10707  175 GMTAGIIREL 184

nudix hydrolase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  40 ILFTKRAAHLRHHPGEVCFPGGMWEPGDDNLLVTAQREVHEEIGLPAGHIQLLGALPQSHTRAGTAVTPFVA--HFDASI 117
Cdd:PLN02709   53 VILTKRSSTLSSHPGEVALPGGKRDEEDKDDIATALREAREEIGLDPSLVTIISVLEPFVNKKGMSVAPVIGflHDKKAF 132

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1150411341 118 NLQPSPDELESIFMVPLAAFQAGLQVREDHFERHGHILRVPVYHY------QGYEIWGFTAAVTAQLLRLVDRAL 186
Cdd:PLN02709  133 KPLPNPAEVEEIFDVPLEMFLKDKNKRAEEREHEGERYLLQYFDYysedkeRNFIIWALTAGILIRVASIVYQRL 207

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 1150411341  24 PQAAVLVLISRGDNpsILFTKRAahlrHHP--GEVCFPGGMWEPGDdNLLVTAQREVHEEIGLPAGHIQLLGALPQSHTR 101
Cdd:cd04681     5 VAAAVGVIIRNEGE--ILFVRRA----KEPgkGKLDLPGGFVDPGE-SAEEALRRELREELGLKIPKLRYLCSLPNTYLY 77

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1150411341 102 AG----TAVTPFVAHFDASINLQPSPDELESIFMVPLA 135
Cdd:cd04681    78 KGitykTCDLFFTAELDEKPKLKKAEDEVAELEWLDLE 115

nucleoside diphosphate-linked moiety X)) motif 17; Nucleoside diphosphate-linked moiety X)) motif 17 (EC 3.6.1.-) encoded by the NUDT17 gene on chromosome 1q21.1 and encodes an enzyme thought to hydrolyse some nucleoside diphosphate derivatives. Members of the NUDIX hydrolase superfamily catalyze 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 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  27 AVLVLISRGDNpSILFTKRAAHLRHHPGEVCFPGGMWEPGDDnLLVTAQREVHEEIGL---PAGHIQLLGA--------- 94
Cdd:cd04694     4 GVVVLIEDSDD-RVLLTRRAKHMRTFPGVWVPPGGHVELGES-LLEAGLRELQEETGLevsDIQSLSLLGLwesvyptll 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1150411341  95 ---LPQSHTRA-GTAVTPFVAHFDaSINLQPSPDELESIFMVP 133
Cdd:cd04694    82 sigLPKRHHIVvYYLVKLSESHEN-QEQLKLQEDEVDAAVWLP 123

ADP-ribose pyrophosphatase, UDP-glucose pyrophosphatase, and similar proteins; ADP-ribose pyrophosphatase (ADPRase) ( NUDIX (Nucleoside diphosphate-linked moiety X)) motif 5; Nudt5) catalyzes the hydrolysis of ADP-ribose and a variety of additional ADP-sugar conjugates to AMP and ribose-5-phosphate. In humans, there are four distinct ADPRase activities, three putative cytosolic enzymes (ADPRase-I, -II, and -Mn) and a single mitochondrial enzyme (ADPRase-m). Human ADPRase-II is also referred to as NUDT5. It lacks the N-terminal target sequence unique to mitochondrial ADPRase. The different cytosolic types are distinguished by their specificities for substrate and specific requirement for metal ions. NUDT5 forms a homodimer. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site. In addition to the NUDIX motif, there are additional conserved amino acid residues, distal from the signature sequence, that correlate with substrate specificity. UDP-glucose pyrophosphatase (UGPPase) (EC 3.6.1.45; also known as nucleoside diphosphate-linked moiety X)) motif 14; Nudt14) hydrolyzes the pyrophosphate of the nucleoside diphosphate sugar to generate glucose-1-P and UMP. In mammals, UDP-glucose is the glucosyl donor for the synthesis of the storage polysaccharide glycogen. UGPPase, as a regulator of UDP-glucose, could play a regulatory role, but it has been shown to prefer ADP-ribose over UDP-glucose. Like other members of the NUDIX hydrolase superfamily, it requires a divalent cation, such as Mg2+, for its activity. It also contains a highly conserved 23-residue NUDIX motif (GX5EX7REUXEEXGU, where U = I, L or V) which functions as a metal binding site/catalytic site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  27 AVLVLISRGDNpSILFTKraaHLRHHPGEVC--FPGGMWEPGDDnLLVTAQREVHEEIGLPAGHIQLLGALPQSHTRAGT 104
Cdd:cd03424     4 AVAVLAITDDG-KVVLVR---QYRHPVGRVLleLPAGKIDPGED-PEEAARRELEEETGYTAGDLELLGSFYPSPGFSDE 78

                          90       100
                  ....*....|....*....|....*
gi 1150411341 105 AVTPFVAHfDASINLQPSPDELESI 129
Cdd:cd03424    79 RIHLFLAE-DLTPVSEQALDEDEFI 102

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1150411341  20 PVSSPQAAVLVLISRGDnpsILFTKRAahlrhHPGEVCFPGGMWEPGDdNLLVTAQREVHEEIGLPAGHIQLLG 93
Cdd:cd04677     9 PLILVGAAVIILNEQGR---ILLQKRT-----DTGDWGLPGGAMELGE-SLEETARREVFEETGLTVEELELLG 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  34 RGDNPSILFtkraahlrhhPGEVCFPGGMWEPGDdNLLVTAQREVHEEIGLPAGHIQLLG 93
Cdd:cd18882    20 RDDKPGIPY----------PGYWGLFGGHLEPGE-TPEEAIRRELEEEIGYEPGEFRFFL 68

MutT homolog 2; MutT Homolog 2 (MTH2; EC 3.6.1.9), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 15/Nudt15, may catalyze the hydrolysis of nucleoside diphosphates, triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP, and prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP. MTH2 may also play a role in DNA synthesis and cell cycle progression by stabilizing PCNA. Members of the NUDIX hydrolase superfamily catalyze 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 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  24 PQAAVLVLISRGDNpSILFTKRAAhlRHHPGEVCFPGGMWEPGDDnLLVTAQREVHEEIGLPAGHIQLLGALPQSHTRAG 103
Cdd:cd04678     1 PRVGVGVIVLNDDG-KVLLGRRKG--SHGAGTWALPGGHLEFGES-FEECAAREVLEETGLEIRNVRFLTVTNDVFEEEG 76

                  ....*...
gi 1150411341 104 -TAVTPFV 110
Cdd:cd04678    77 kHYVTIFV 84

NAD(+) diphosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  18 SYPVSSPqaAVLVLISRGDnpSILFtkrAAHLRHhpgevcfPGGMW-------EPGDdNLLVTAQREVHEEIGLPAGHIQ 90
Cdd:PRK00241  127 YYPRIAP--CIIVAVRRGD--EILL---ARHPRH-------RNGVYtvlagfvEVGE-TLEQCVAREVMEESGIKVKNLR 191

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1150411341  91 LLG----ALPQShtragtAVTPFVAHFDaSINLQPSPDELES 128
Cdd:PRK00241  192 YVGsqpwPFPHS------LMLGFHADYD-SGEIVFDPKEIAD 226

MutT homolog-1 and similar proteins; MutT homolog-1 (MTH1), also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 1/Nudt1, is a member of the NUDIX hydrolase superfamily. MTH1, the mammalian counterpart of MutT, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-ATP, to monophosphates, thereby preventing the incorporation of such oxygen radicals during replication. This is an important step in the repair mechanism in genomic and mitochondrial DNA. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity, and contain 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. MTH1 is predominantly localized in the cytoplasm and mitochondria. Structurally, this enzyme adopts a similar fold to MutT despite low sequence similarity outside the conserved NUDIX motif. The most distinctive structural difference between MutT and MTH1 is the presence of a beta-hairpin, which is absent in MutT. This results in a much deeper and narrower substrate binding pocket. Mechanistically, MTH1 contains dual specificity for nucleotides that contain 2-OH-adenine bases and those that contain 8-oxo-guanine bases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  29 LVLISRGDnpSILFTKRAAhlRHHPGEVCFPGGMWEPGDDnLLVTAQREVHEEIGLPAGHIQLLGAL----PQSHTRAGT 104
Cdd:cd18886     4 LCFIIRDD--EVLLLNRNK--KPNMGKWNGVGGKLEPGES-PEECAIREVFEETGLELEDLQLRGIVtfpsFDGGEDWLM 78

                          90       100
                  ....*....|....*....|.
gi 1150411341 105 AVtpFVAHFDASiNLQPSPDE 125
Cdd:cd18886    79 YV--FLAEAFSG-ELVESDRE 96

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 1150411341  27 AVLVLISRGDNPSILFTKRAAHLRHHPGevcfpggMW--------EPGDDnLLVTAQREVHEEIGLPAGHIQL--LGALP 96
Cdd:cd04692    28 TVHVWLVNPEEGRLLLQKRSANKDDFPG-------LWdisaaghiDAGET-YEEAAVRELEEELGLTVSPEDLifLGVIR 99

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1150411341  97 QSHtRAGTA-----VTPFVAHFDASIN-LQPSPDELESIFMVPL 134
Cdd:cd04692   100 EEV-IGGDFidnefVHVYLYETDRPLEeFKLQPEEVAGVVFVDL 142

plant diadenosine tetraphosphate (Ap4A) hydrolase and similar proteins; Diadenosine tetraphosphate (Ap4A) hydrolase is a member of the NUDIX hydrolase superfamily. Members of this family are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one group (represented by this subfamily) and fungi/animals/archaea enzymes fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for the inhibition of such invasive bacteria. Besides the signature NUDIX motif (G[X5]E[X7]REUXEEXGU where U is Ile, Leu, or Val), Ap4A hydrolase is structurally similar to the other members of the NUDIX hydrolase superfamily with some degree of variations. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1150411341  58 FP-GGMwEPGDDnLLVTAQREVHEEIGLPAGHIQLLGALP 96
Cdd:cd03671    31 FPqGGI-DEGED-PEEAALRELYEETGLSPEDVEIIAETP 68

bifunctional NMN adenylyltransferase/ADP-ribose pyrophosphatase and similar proteins; Bacterial NadM-Nudix is a bifunctional enzyme containing a nicotinamide mononucleotide (NMN) adenylyltransferase (NMNAT) and an ADP-ribose pyrophosphatase (ADPRase) domain. NMNAT was initially identified as an NAD+ synthase that catalyzes the reversible conversion of NMN to NAD+ in the final step of both the de novo biosynthesis and salvage pathways in most organisms across all three kingdoms of life ADPRase is a member of the NUDIX family proteins, catalyzes the metal-induced and concerted general acid-base hydrolysis of ADP ribose (ADPR) into AMP and ribose-5'-phosphate (R5P). Additional members in this cd include bacterial transcriptional regulator, NrtR, which represses the transcription of NAD biosynthetic genes in vitro and adenosine diphosphate ribose (ADPR), as well as NadQ, a NUDIX-like ATP-responsive regulator of NAD biosynthesis. 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, U=I, L or V) which functions as 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 _ "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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1150411341  28 VLVLISRGDNPSILFTKRAAHlrHHPGEVCFPGGMWEPGDDnLLVTAQREVHEEIGLPAGHIQLLGA 94
Cdd:cd18873     7 CVIFGFDDGELKVLLIKRKNE--PFKGGWALPGGFVREDET-LEDAARRELREETGLKDIYLEQLGT 70

Predicted NTP pyrophosphohydrolase, NUDIX family [Nucleotide transport and metabolism, General function prediction only];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1150411341  59 PGGMWEPGDDnLLVTAQREVHEEIGL--PAGHIQLLGALPQshtRAGTAVTPFVAHFD 114
Cdd:COG4119    41 PKGEYEPGED-PLAAARREFAEETGVpaPDGPFIPLGEVRQ---KSGKVVTAWAVEGD 94

NADH pyrophosphatase; NADH pyrophosphatase, also known as NUDIX (nucleoside diphosphate linked moiety X)) motif 13/Nudt13, is thought to have NADH pyrophosphatase activity, be involved in NADH metabolic process and NADP catabolic process, catalyzing the cleavage of NADH into reduced nicotinamide mononucleotide (NMNH) and AMP, and located in mitochondrion. Like other members of the NUDIX family, it requires a divalent cation, such as Mg2+ or Mn2+, for activity. Members of this family are also recognized by 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. A block of 8 conserved amino acids downstream of the NUDIX motif is thought to give NADH pyrophosphatase its specificity for NADH. NADH pyrophosphatase forms a dimer.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1150411341  27 AVLVLISRGDNpSILftkraahLRHHPGevcFPGGMW-------EPGDdNLLVTAQREVHEEIGLPAGHIQLLG 93
Cdd:cd03429     3 AVIVLVTNGED-KIL-------LARQPR---WPPGRYsllagfvEPGE-TLEEAVRREVKEEVGLRVKNVRYVG 64

bifunctional nicotinamide-nucleotide adenylyltransferase/Nudix hydroxylase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  59 PGGMWEPgDDNLLVTAQREVHEEIGLPAGHIQLLGALPQSHT--------RAGTAVTPFVAHFDA----SINLQPSPDEl 126
Cdd:PRK05379  233 PGGFLEQ-DETLLDACLRELREETGLKLPEPVLRGSIRDQQVfdhpgrslRGRTITHAFLFEFPAgelpRVKGGDDADK- 310

                          90       100
                  ....*....|....*....|....*....
gi 1150411341 127 esIFMVPLAAFqagLQVREDHFERHGHIL 155
Cdd:PRK05379  311 --ARWVPLAEL---LAMRDRMFEDHFQII 334

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 1150411341  30 VLISRGDnpSILFTKRAahlrhhPGEVCFPGGMWEPGDDnLLVTAQREVHEEIGLPAGHIQLLGALPQSHTRagtavtPF 109
Cdd:cd04667     5 VICRRGD--RILLVARR------GGRWLLPGGKIEPGES-PLEAAIRELKEETGLAALSLLYLFEHEGPHKL------HH 69

                          90
                  ....*....|....
gi 1150411341 110 VAHFDASINLQPSP 123
Cdd:cd04667    70 VFLAEAPDGGRPRP 83

nucleoside diphosphate-linked moiety X)) motif 16; U8 SnoRNA-decapping enzyme, also known as NUDIX (nucleoside diphosphate-linked moiety X)) motif 16/Nudt16, is encoded by the human NUDT16 gene and a RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. Members of the NUDIX hydrolase superfamily catalyze 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 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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150411341  52 HPGEVCFPGGMWEPGDDnLLVTAQREVHEEIGL-----PAGHIQLLGALPQSHTRAgtavtpFVAHFDAsINLQpspdeL 126
Cdd:cd18869    34 FDGLLGFPGGFVDTGES-LEEGLNRELREELGLahavfPVTEDDYRSSHVREGPKR------LVLHFYA-KELS-----L 100

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1150411341 127 ESIFMVPLAAFQAglqvrEDH-FERHGHIlRVPVY 160
Cdd:cd18869   101 EELDEIEIAAVNA-----KDHgLEVLGLI-RVPLY 129