Elucidation of succinyl transferase reaction mechanisms which is difficult to perform by organic synthesis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23710277
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Japan Synchrotron Radiation Research Institute
• Principal Investigator: OKUMURA Hideo 公益財団法人高輝度光科学研究センター, 利用研究促進部門, 研究員 (90377903)
• Project Period (FY): 2011 – 2012
• Keywords: X線結晶構造解析 / ケミカルバイオロジー / エステル化反応 / 基質認識

Research Abstract

New enzymes which modify the polyketide compounds have been discovered by the identification of gene cluster of Streptomyces which produce reveromycin A expected as an osteoporotic therapeutic drug candidate. In the gene cluster, the enzyme which catalyzes the biosynthesis reaction that transfers a succinyl group to tertiary alcohol was found. And it is revealed that this enzyme conducts a difficult reaction by organic synthesis under physiological environment. This investigation was intended to elucidate the details of the reaction mechanism with this enzyme by X-ray crystal structure analysis. By the crystallization condition search, the enzyme crystals were obtained. And as the result of the diffraction experiments in synchrotron facility, the diffraction data achieve to 1.8 A resolution was obtained. By the progress of structure analysis of obtained data, it is expected that the details of the structure of the enzyme become clear and the reaction mechanism is elucidate in future.