coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958  63 KYSVLLPLLARGEKLYLLFTVRSDKLRRAPGEVCFPGGKRDPVDADDTATALREAQEEVGLHPHQVEVVSHLVPYFInky 142
Cdd:cd03426     2 RAAVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYT--- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958 143 alsnivpfsvdvtsfpcpqqeeRNNDLVTPVVGFLDPDFQAQPNADEVKDVFLVPLDYFLCPQVYYQSHFTHSG--YHFV 220
Cdd:cd03426    79 ----------------------PSGFVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGprGTYR 136

                         170       180
                  ....*....|....*....|.
gi 1958746958 221 LHCFEYTDpetgskYLIKGMT 241
Cdd:cd03426   137 VPFYPYEG------YVIWGLT 151

coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958  63 KYSVLLPLLARGEKLYLLFTVRSDKLRRAPGEVCFPGGKRDPVDADDTATALREAQEEVGLHPHQVEVVSHLVPYFInky 142
Cdd:cd03426     2 RAAVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYT--- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958 143 alsnivpfsvdvtsfpcpqqeeRNNDLVTPVVGFLDPDFQAQPNADEVKDVFLVPLDYFLCPQVYYQSHFTHSG--YHFV 220
Cdd:cd03426    79 ----------------------PSGFVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGprGTYR 136

                         170       180
                  ....*....|....*....|.
gi 1958746958 221 LHCFEYTDpetgskYLIKGMT 241
Cdd:cd03426   137 VPFYPYEG------YVIWGLT 151

8-oxo-dGTP pyrophosphatase MutT and related house-cleaning NTP pyrophosphohydrolases, NUDIX family [Defense mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958  54 TRYSHLSPSkySVLLPLLARGEklyLLFTVRSDKlRRAPGEVCFPGGKrdpVDADDT--ATALREAQEEVGLHPHQVEVV 131
Cdd:COG0494     7 SEPEHYRPA--VVVVLLDDDGR---VLLVRRYRY-GVGPGLWEFPGGK---IEPGESpeEAALRELREETGLTAEDLELL 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958746958 132 SHLV-PYFINKYalsnIVPFsvdvtsfpcpqqeernndlvtpVVGFLDPDFQAQPNA-DEVKDVFLVPLDYFL 202
Cdd:COG0494    78 GELPsPGYTDEK----VHVF----------------------LARGLGPGEEVGLDDeDEFIEVRWVPLDEAL 124

coenzyme A pyrophosphatase and similar proteins; Coenzyme A pyrophosphatase (CoAse; EC 3.6.1.1), also called nucleoside diphosphate-linked moiety X)) motif 7, is a member of the NUDIX hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved NUDIX fold and requires a single divalent cation for catalysis. In addition to a signature NUDIX motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid sythesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958  63 KYSVLLPLLARGEKLYLLFTVRSDKLRRAPGEVCFPGGKRDPVDADDTATALREAQEEVGLHPHQVEVVSHLVPYFInky 142
Cdd:cd03426     2 RAAVLIPLVEGDGELHVLLTKRASHLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYT--- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958 143 alsnivpfsvdvtsfpcpqqeeRNNDLVTPVVGFLDPDFQAQPNADEVKDVFLVPLDYFLCPQVYYQSHFTHSG--YHFV 220
Cdd:cd03426    79 ----------------------PSGFVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGprGTYR 136

                         170       180
                  ....*....|....*....|.
gi 1958746958 221 LHCFEYTDpetgskYLIKGMT 241
Cdd:cd03426   137 VPFYPYEG------YVIWGLT 151

nudix hydrolase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958  58 HLSPSKYSVLLPLLA--RGEK--LYLLFTVRSDKLRRAPGEVCFPGGKRDPVDADDTATALREAQEEVGLHPHQVEVVSH 133
Cdd:PLN02709   28 HFPAKSSAVLVCLYQeqREDKneLRVILTKRSSTLSSHPGEVALPGGKRDEEDKDDIATALREAREEIGLDPSLVTIISV 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958 134 LVPyFINKYALSnivpfsvdvtsfpcpqqeernndlVTPVVGFL--DPDFQAQPNADEVKDVFLVPLDYFLCPQVYYQSH 211
Cdd:PLN02709  108 LEP-FVNKKGMS------------------------VAPVIGFLhdKKAFKPLPNPAEVEEIFDVPLEMFLKDKNKRAEE 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1958746958 212 FTHSGYHFVLHCFEYTDPETGSKYLIKGMTSKLAVLAALIIFEKSPSFE 260
Cdd:PLN02709  163 REHEGERYLLQYFDYYSEDKERNFIIWALTAGILIRVASIVYQRLPEFQ 211

NUDIX domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958746958  71 LARGEKLYLLFTVRSDklRRAPGEVCFPGGKrdpVDADDT--ATALREAQEEVGLHPHQVEVVSHLVPYF 138
Cdd:pfam00293   9 VLLNEKGRVLLVRRSK--KPFPGWWSLPGGK---VEPGETpeEAARRELEEETGLEPELLELLGSLHYLA 73

ADP-ribose pyrophosphatase YjhB, NUDIX family [Nucleotide transport and metabolism];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958746958  73 RGEKLYLLFTVRSDKLRraPGEVCFPGGKrdpVDADDT--ATALREAQEEVGLHPHQVEVV 131
Cdd:COG1051    14 FRKDGRVLLVRRADEPG--KGLWALPGGK---VEPGETpeEAALRELREETGLEVEVLELL 69

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
                  ....*....|....*....|....*....|....*....|..
gi 1958746958  92 PGEVCFPGGKRDpvdADDTA--TALREAQEEVGLHPHQVEVV 131
Cdd:cd18877    46 GGTWALPGGARD---SGETPeaAALRETEEETGLDADTLRVV 84

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 1958746958  79 LLFTVRSdklrRAP--GEVCFPGGKrdpVDADDTA--TALREAQEEVGLHPHQVEvvshlvpYFinkYALSNIVPFSvDV 154
Cdd:cd04681    19 ILFVRRA----KEPgkGKLDLPGGF---VDPGESAeeALRRELREELGLKIPKLR-------YL---CSLPNTYLYK-GI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1958746958 155 TSFPCpqqeernnDLVtpVVGFLDPDFQAQPNADEVKDVFLVPLD 199
Cdd:cd04681    81 TYKTC--------DLF--FTAELDEKPKLKKAEDEVAELEWLDLE 115

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
                  ....*....|....*....|....*..
gi 1958746958  97 FPGGKRDPvDADDTATALREAQEEVGL 123
Cdd:cd04690    27 LPGGKREP-GETPLQALVRELKEELGL 52

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
                  ....*....|....*....|....*....|....*....|....*
gi 1958746958  98 PGGKrdpVDADDT--ATALREAQEEVGLHPHQVEVVSHlVPYFIN 140
Cdd:cd03674    30 PGGH---VEPDEDplEAALREAREETGLDVELLSPLSP-DPLDID 70

MutT homolog-1 (MTH1); MutT homolog-1 (MTH1; EC 3.6.1.- ), also called 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
                  ....*....|....*....|....*....|....*....|....*.
gi 1958746958  98 PGGKrdpVDADDT--ATALREAQEEVGLHPHQVEVVSHLVPYFINK 141
Cdd:cd03427    32 FGGK---VEPGETieEAAVRELEEEAGLTATELEKVGRLKFEFPDD 74