The serine acetyltransferase reaction: acetyl transfer from an acylpantothenyl donor to an alcohol.
Serine acetyltransferase is a member of the left-handed parallel beta-helix family of enzymes that catalyzes the committed step in the de novo synthesis of l-cysteine in bacteria and plants. The enzyme has an ordered kinetic mechanism with acetyl CoA bound prior to l-serine and O-acetyl-l-serine released prior to CoA. The rate-limiting step along the reaction pathway is the nucleophilic attack of the serine hydroxyl on the thioester of acetyl CoA. Product release contributes to rate-limitation at saturating concentrations of reactants. The reaction is catalyzed by an active site general base with a pK of 7, which accepts a proton from the serine hydroxyl as a tetrahedral intermediate is formed between the reactants, and donates it to the thiol of CoA as the intermediate collapses to give products. This mechanism is likely the same for all O-acyltransferases that catalyze their reaction by direct attack of the alcohol on the acyl donor, using an active-site histidine as the general base. Serine acetyltransferase is regulated by feedback inhibition by the end product l-cysteine, which acts by binding to the serine site in the active site and inducing a conformational change that prevents reactant binding. The enzyme also associates with O-acetylserine sulfhydrylase, the final enzyme in the biosynthetic pathway, which contributes to stabilizing the acetyltransferase.
Johnson
Corey M
CM
Department of Chemistry and Biochemistry, University of Oklahoma, 620 Parrington Oval, Norman, OK 73019, USA.
Roderick
Steven L
SL
Cook
Paul F
PF
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000438:Alcohols / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D003545:Cysteine / Q000378:metabolism; D004795:Enzyme Stability; D025461:Feedback, Physiological; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D008961:Models, Structural; D015394:Molecular Structure; D008970:Molecular Weight; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012694:Serine / Q000378:metabolism; D051050:Serine O-Acetyltransferase; D013379:Substrate Specificity
D000438:Alcohols; D012694:Serine; D006639:Histidine; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; D051050:Serine O-Acetyltransferase; D003545:Cysteine