The 1.75 Å Crystal Structure of Acetyl-CoA Synthetase Bound to Adenosine-5'-propylphosphate and Coenzyme A

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• 作者：Andrew M. Gulick ; Vincent J. Starai ; Alexander R. Horswill ; Kristen M. Homick ; and Jorge C. Escalante-Semerena
• 刊名：Biochemistry
• 出版年：2003
• 出版时间：March 18, 2003
• 年：2003
• 卷：42
• 期：10
• 页码：2866 - 2873
• 全文大小：604K
• 年卷期：v.42,no.10(March 18, 2003)
• ISSN：1520-4995

文摘

Acetyl-coenzyme A synthetase catalyzes the two-step synthesis of acetyl-CoA from acetate,ATP, and CoA and belongs to a family of adenylate-forming enzymes that generate an acyl-AMPintermediate. This family includes other acyl- and aryl-CoA synthetases, firefly luciferase, and theadenylation domains of the modular nonribosomal peptide synthetases. We have determined the X-raycrystal structure of acetyl-CoA synthetase complexed with adenosine-5'-propylphosphate and CoA. Thestructure identifies the CoA binding pocket as well as a new conformation for members of this enzymefamily in which the ~110-residue C-terminal domain exhibits a large rotation compared to structures ofpeptide synthetase adenylation domains. This domain movement presents a new set of residues to theactive site and removes a conserved lysine residue that was previously shown to be important for catalysisof the adenylation half-reaction. Comparison of our structure with kinetic and structural data of closelyrelated enzymes suggests that the members of the adenylate-forming family of enzymes may adopt twodifferent orientations to catalyze the two half-reactions. Additionally, we provide a structural explanationfor the recently shown control of enzyme activity by acetylation of an active site lysine.