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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1vr7
Original Entry
Title:
Lyase
Compound:
S-adenosylmethionine decarboxylase proenzyme
Mutant:
No
UniProt/Swiss-Prot:
Q9WZC3-S
Q9WZC3-S
EC Class:
4.1.1.50
Other CSA Entries:
Overview of all sites for 1vr7
Homologues of 1vr7
Entries for UniProt/Swiss-Prot: Q9WZC3
Entries for UniProt/Swiss-Prot: Q9WZC3
Entries for EC: 4.1.1.50
Other Databases:
PDB entry: 1vr7
PDBsum entry: 1vr7
UniProt/Swiss-Prot: Q9WZC3
UniProt/Swiss-Prot: Q9WZC3
IntEnz entry: 4.1.1.50
Literature Report:
Introduction:
S-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.

Mechanism:
Nonhydrolytic 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.

Sites:

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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
SERA 55 55Sidechain
ElectrostaticTransition state
Ser55 is thought to stabilise the oxyoxazolidine intermediate in nonhydrolytic serinolysis by forming a hydrogen bond to the exocyclic oxygen.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15150268 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 11583148 Related protein: UniProt P17707 Structural similarity to homologue of known mechanism
PubMed ID 15150268 Current protein Conservation of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
SERA 63 63Sidechain
NucleophileResidue
ModifiedSubstrate
ModifiedWater
Ser63 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.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15184017 Related protein: UniProt P56065 Structural similarity to homologue of known mechanism
PubMed ID 15150268 Current protein Mutagenesis of residue
PubMed ID 11583148 Related protein: UniProt P17707 Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 68 68Sidechain
Acid/baseResidue
His68 removes the C-alpha proton from Ser63 in the ester intermediate during nonhydrolytic serinolysis. This causes beta-elimination and strand cleavage.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11583148 Related protein: UniProt P17707 Structural similarity to homologue of known mechanism
PubMed ID 15150268 Current protein Mutagenesis of residue
PubMed ID 15150268 Current protein Conservation of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
CYSA 83 83Sidechain
ElectrostaticTransition state
Acid/baseSubstrate
Cys83 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.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15150268 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 11583148 Related protein: UniProt P17707 Structural similarity to homologue of known mechanism
PubMed ID 15150268 Current protein Conservation of residue
PubMed ID 10029540 Related protein: UniProt P17707 Structural similarity to homologue of known mechanism
Notes:


References:
Which EBI biological databases are available and how do I access them? EBI Site Map