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Catalytic Site Atlas

CSA LITERATURE entry for 1vr7

E.C. nameadenosylmethionine decarboxylase
SpeciesThermotoga maritima (Bacteria)
E.C. Number (IntEnz) 4.1.1.50
CSA Homologues of 1vr7
CSA Entries With UniProtID Q9WZC3
CSA Entries With EC Number 4.1.1.50
PDBe Entry 1vr7
PDBSum Entry 1vr7
MACiE Entry M0225

Literature Report

IntroductionS-adenosylmethionine decarboxylase (AdoMetDC) isolated from Thermotoga maritima is an enzyme that catalyses the decarboxylation of S-adenosylmethionine (AdoMet or SAM) to S-adenosyl-5'-(3-methylthiopropylamine) (dcAdoMet). AdoMetDC is regulatory enzyme in the biosynthesis of spermine and spermidine. It is a class 1B AdoMetDC and belongs to a small family of decarboxylating enzymes that act on amino acids using bound pyruvate as an electron sink. AdoMetDC is synthesised as a proenzyme and must undergo self-maturation by nonhydrolytic serinolysis. It is during this process that the pyruvate group is formed at the carboxy terminus of the alpha chain.
MechansimNonhydrolytic serinolysis: Ser63 acts as a nucleophile and attacks the carbonyl of Glu62. The oxyoxazolidine intermediate rearranges into an ester intermediate. His68 removes the C-alpha proton from Ser63 causing beta-elimination to form the C-terminus of the beta-chain and the terminal dehydroalanine residue of the alpha chain. The latter tautomerises into an imine and is hydrolysed to form the terminal pyruvoyl residue of the alpha-chain.
AdoMet decarboxylation: the pyruvoyl prosthetic group forms a Schiff base with the alpha-amino group of AdoMet. This prompts the loss of the alpha-carboxylate to form an extended enolate system with the negative charge residing on the amide oxygen of the pyruvoyl group. The carbonyl reforms and the alpha-carbon of the intermediate accepts a proton from Cys83. The Schiff base is then hydrolysed and dcAdoMet is released.
Reaction

Catalytic Sites for 1vr7

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA6868macie:sideChainHis68 removes the C-alpha proton from Ser63 in the ester intermediate during nonhydrolytic serinolysis. This causes beta-elimination and strand cleavage.
CysA8383macie:sideChainCys83 may stabilise the formation of the oxyoxazolidine intermediate in nonhydrolytic serinolysis through a hydrogen bond to the exocyclic oxygen. Cys83 acts a proton donor for the decarboxylated Schiff base during AdoMet decarboxylation.
SerA5555macie:sideChainSer55 is thought to stabilise the oxyoxazolidine intermediate in nonhydrolytic serinolysis by forming a hydrogen bond to the exocyclic oxygen.
SerA6363macie:sideChainSer63 is the nucleophile for the protocleavage reaction and is subsequently converted to a pyruvoyl residue. It forms a Schiff base with the alpha-amino group of SAM, prompting decarboxylation. The Schiff base is then hydrolysed.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB6868macie:sideChainHis68 removes the C-alpha proton from Ser63 in the ester intermediate during nonhydrolytic serinolysis. This causes beta-elimination and strand cleavage.
CysB8383macie:sideChainCys83 may stabilise the formation of the oxyoxazolidine intermediate in nonhydrolytic serinolysis through a hydrogen bond to the exocyclic oxygen. Cys83 acts a proton donor for the decarboxylated Schiff base during AdoMet decarboxylation.
SerB5555macie:sideChainSer55 is thought to stabilise the oxyoxazolidine intermediate in nonhydrolytic serinolysis by forming a hydrogen bond to the exocyclic oxygen.
SerB6363macie:sideChainSer63 is the nucleophile for the protocleavage reaction and is subsequently converted to a pyruvoyl residue. It forms a Schiff base with the alpha-amino group of SAM, prompting decarboxylation. The Schiff base is then hydrolysed.

Literature References

Notes:
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