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 779927949  13 KLRRAPGEVCFPGGKRDPVDADDTATALREAQEEVGLHPHQVEVVSHLVPYFINNNDLVTPVVGFLDPDFQAQPNADEVK 92
Cdd:cd03426   26 HLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGFVVTPFVGLLDDPPPLRPNPDEVA 105

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 779927949  93 DVFLVPLDYFLCPQVYYQSHFTHSG--YHFVLHCFEYTDpetgskYLIKGMT 142
Cdd:cd03426  106 EVFTVPLSFLLDPEPRRYETFLRSGprGTYRVPFYPYEG------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 779927949  13 KLRRAPGEVCFPGGKRDPVDADDTATALREAQEEVGLHPHQVEVVSHLVPYFINNNDLVTPVVGFLDPDFQAQPNADEVK 92
Cdd:cd03426   26 HLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGFVVTPFVGLLDDPPPLRPNPDEVA 105

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 779927949  93 DVFLVPLDYFLCPQVYYQSHFTHSG--YHFVLHCFEYTDpetgskYLIKGMT 142
Cdd:cd03426  106 EVFTVPLSFLLDPEPRRYETFLRSGprGTYRVPFYPYEG------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 779927949  18 PGEVCFPGGKrdpVDADDT--ATALREAQEEVGLHPHQVEVVSHLV-PYFINNndLVTPVVG-FLDPDFQAQPNA-DEVK 92
Cdd:COG0494   39 PGLWEFPGGK---IEPGESpeEAALRELREETGLTAEDLELLGELPsPGYTDE--KVHVFLArGLGPGEEVGLDDeDEFI 113

                         90
                 ....*....|.
gi 779927949  93 DVFLVPLDYFL 103
Cdd:COG0494  114 EVRWVPLDEAL 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 779927949  13 KLRRAPGEVCFPGGKRDPVDADDTATALREAQEEVGLHPHQVEVVSHLVPYFINNNDLVTPVVGFLDPDFQAQPNADEVK 92
Cdd:cd03426   26 HLRSHPGQIAFPGGKREPGDESPVETALRETEEEIGLPPESVEVLGRLDPLYTPSGFVVTPFVGLLDDPPPLRPNPDEVA 105

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 779927949  93 DVFLVPLDYFLCPQVYYQSHFTHSG--YHFVLHCFEYTDpetgskYLIKGMT 142
Cdd:cd03426  106 EVFTVPLSFLLDPEPRRYETFLRSGprGTYRVPFYPYEG------YVIWGLT 151

nudix hydrolase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 779927949  14 LRRAPGEVCFPGGKRDPVDADDTATALREAQEEVGLHPHQVEVVSHLVPyFINNNDL-VTPVVGFL--DPDFQAQPNADE 90
Cdd:PLN02709  62 LSSHPGEVALPGGKRDEEDKDDIATALREAREEIGLDPSLVTIISVLEP-FVNKKGMsVAPVIGFLhdKKAFKPLPNPAE 140

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 779927949  91 VKDVFLVPLDYFLCPQVYYQSHFTHSGYHFVLHCFEYTDPETGSKYLIKGMTSKLAVLAALIIFEKSPSFE 161
Cdd:PLN02709 141 VEEIFDVPLEMFLKDKNKRAEEREHEGERYLLQYFDYYSEDKERNFIIWALTAGILIRVASIVYQRLPEFQ 211

NUDIX domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 779927949   13 KLRRAPGEVCFPGGKrdpVDADDT--ATALREAQEEVGLHPHQVEVVSHL------VPYFINNNDLVTPVVGFLDPDFQA 84
Cdd:pfam00293  23 SKKPFPGWWSLPGGK---VEPGETpeEAARRELEEETGLEPELLELLGSLhylapfDGRFPDEHEILYVFLAEVEGELEP 99

                          90
                  ....*....|....*.
gi 779927949   85 QPNaDEVKDVFLVPLD 100
Cdd:pfam00293 100 DPD-GEVEEVRWVPLE 114

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 779927949  15 RRAPGEVCFPGgKRD-------PVDADDTATALREAQEEVGLHP----HQVEVVSHLVPYFINNNDLVTPVVGF-----L 78
Cdd:cd03676   27 RRSATKATYPG-KLDnlvaggvPAGESPLETLVREAEEEAGLPEdlarQARPAAGRVSYFYRSDEGGLQPEVLYvydleL 105

                         90       100
                 ....*....|....*....|..
gi 779927949  79 DPDFQAQPNADEVKDVFLVPLD 100
Cdd:cd03676  106 PEDFVPKPQDGEVESFELMSVD 127

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 779927949  18 PGEVCFPGGKRDpvdADDTA--TALREAQEEVGLHPHQVEVV 57
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
                 ....*....|....*....|....*..
gi 779927949  23 FPGGKRDPvDADDTATALREAQEEVGL 49
Cdd:cd04690   27 LPGGKREP-GETPLQALVRELKEELGL 52

ADP-ribose pyrophosphatase; ADP-ribose pyrophosphatase (ADPRase) (also known as 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 779927949  23 FPGGKrdpVDADDTA--TALREAQEEVGLHPHQVEVVSHLV---PYFINNN-DLVTPVVGFLDPDFQ---AQPNADEVKD 93
Cdd:cd18888   37 FPAGL---VDPGESPeqAALRELKEETGYTGEKVLSVSPPLaldPGLSNANmKLVTVEVDGDDPENQnpkQELEDGEFIE 113

                         90
                 ....*....|
gi 779927949  94 VFLVPLDYFL 103
Cdd:cd18888  114 VILVPLNELL 123

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 779927949  24 PGGKrdpVDADDT--ATALREAQEEVGLHPHQVEVVSHLVPYFINNN 68
Cdd:cd03427   32 FGGK---VEPGETieEAAVRELEEEAGLTATELEKVGRLKFEFPDDP 75