NUDIX hydrolase superfamily; 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 343887378  38 NKYSVLLPLVAKEGKLHLLFTVRSEKP-----------------------------CEVLAPPLPSAMIVSFLRspqkps 88
Cdd:cd03426    1 RRAAVLIPLVEGDGELHVLLTKRASHLrshpgqiafpggkrepgdespvetalretEEEIGLPPESVEVLGRLD------ 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 343887378  89 rrQHHAPctacetTDTLITPFVGLIDHNFQAQPNPAEVKDVFLVPLAYFLHPQVHDQHYVTRLGHRFINHIFEYTNPEdg 168
Cdd:cd03426   75 --PLYTP------SGFVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRGTYRVPFYPYEG-- 144

                        170
                 ....*....|..
gi 343887378 169 vtYQIKGMTANL 180
Cdd:cd03426  145 --YVIWGLTARI 154

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 343887378  38 NKYSVLLPLVAKEGKLHLLFTVRSEKP-----------------------------CEVLAPPLPSAMIVSFLRspqkps 88
Cdd:cd03426    1 RRAAVLIPLVEGDGELHVLLTKRASHLrshpgqiafpggkrepgdespvetalretEEEIGLPPESVEVLGRLD------ 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 343887378  89 rrQHHAPctacetTDTLITPFVGLIDHNFQAQPNPAEVKDVFLVPLAYFLHPQVHDQHYVTRLGHRFINHIFEYTNPEdg 168
Cdd:cd03426   75 --PLYTP------SGFVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRGTYRVPFYPYEG-- 144

                        170
                 ....*....|..
gi 343887378 169 vtYQIKGMTANL 180
Cdd:cd03426  145 --YVIWGLTARI 154

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 343887378  38 NKYSVLLPLVAKEGKLHLLFTVRSEKP-----------------------------CEVLAPPLPSAMIVSFLRspqkps 88
Cdd:cd03426    1 RRAAVLIPLVEGDGELHVLLTKRASHLrshpgqiafpggkrepgdespvetalretEEEIGLPPESVEVLGRLD------ 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 343887378  89 rrQHHAPctacetTDTLITPFVGLIDHNFQAQPNPAEVKDVFLVPLAYFLHPQVHDQHYVTRLGHRFINHIFEYTNPEdg 168
Cdd:cd03426   75 --PLYTP------SGFVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEPRRYETFLRSGPRGTYRVPFYPYEG-- 144

                        170
                 ....*....|..
gi 343887378 169 vtYQIKGMTANL 180
Cdd:cd03426  145 --YVIWGLTARI 154

putative NUDIX hydrolase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 343887378  42 VLLPLVAKEgKLHLLFTVRS----EKPCEVLAP-----PLPSAMIVSFLRSPQK-----PSRRQ---HHAPCTAceTTDT 104
Cdd:PRK10707  34 VLIPIVRRP-QPTLLLTQRSihlrKHAGQVAFPggavdPTDASLIATALREAQEevaipPSAVEvigVLPPVDS--STGY 110

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 343887378 105 LITPFVGLIDHNFQAQPNPAEVKDVFLVPLAYFLHPQVHDQHYVTRLGHRFINHIFEYTNpedgvtYQIKGMTANL 180
Cdd:PRK10707 111 QVTPVVGIIPPDLPYRANEDEVAAVFEMPLAEALHLGRYHPLDIYRRGQSHRVWLSWYEQ------YFVWGMTAGI 180