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 16129767  30 RQAAVLIPIVRRP-QPGLLLTQRSIHLRKHAGQVAFPGGAVDDTDASaiaaalreaeeeVA------------IPPSAVE 96
Cdd:cd03426   1 RRAAVLIPLVEGDgELHVLLTKRASHLRSHPGQIAFPGGKREPGDES------------PVetalreteeeigLPPESVE 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129767  97 VIGVLPPVDSVTGYQVTPVVGIIPPDLPYRASEDEVSAVFEMPLAQALHLG--RYHPLDIYRRGDSHRVWLSWYEQYFVW 174
Cdd:cd03426  69 VLGRLDPLYTPSGFVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEprRYETFLRSGPRGTYRVPFYPYEGYVIW 148

                       170
                ....*....|
gi 16129767 175 GMTAGIIREL 184
Cdd:cd03426 149 GLTARILSEL 158

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 16129767  30 RQAAVLIPIVRRP-QPGLLLTQRSIHLRKHAGQVAFPGGAVDDTDASaiaaalreaeeeVA------------IPPSAVE 96
Cdd:cd03426   1 RRAAVLIPLVEGDgELHVLLTKRASHLRSHPGQIAFPGGKREPGDES------------PVetalreteeeigLPPESVE 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129767  97 VIGVLPPVDSVTGYQVTPVVGIIPPDLPYRASEDEVSAVFEMPLAQALHLG--RYHPLDIYRRGDSHRVWLSWYEQYFVW 174
Cdd:cd03426  69 VLGRLDPLYTPSGFVVTPFVGLLDDPPPLRPNPDEVAEVFTVPLSFLLDPEprRYETFLRSGPRGTYRVPFYPYEGYVIW 148

                       170
                ....*....|
gi 16129767 175 GMTAGIIREL 184
Cdd:cd03426 149 GLTARILSEL 158

Nucleoside diphosphate-linked moiety X)) motif 19; Acyl CoA diphosphohydrolase (also known as NUDIX (nucleoside diphosphate linked moiety X))-type motif 10; Nudt19; testosterone-regulated protein rp2) has activity towards CoA, oxidized CoA and a wide range of CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters. CoA is the major acyl carrier in mammals and a key cofactor in energy metabolism. Dynamic regulation of CoA in different tissues and organs supports metabolic flexibility. 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 16129767  32 AAVLIpIVRRPQPGL--LLTQRSIHLRKHAGQVAFPGGAVDDTDAS 75
Cdd:cd18870   2 AATVI-LLRDGADGLevLLLRRSSTMSFMPGAYVFPGGRVDPADRD 46