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

阐明有机合成难以实现的琥珀酰转移酶反应机制

• 批准号: 23710277
• 负责人: OKUMURA Hideo
• 金额: $ 2.33万
• 依托单位: Japan Synchrotron Radiation Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23710277/
• 关键词: 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; 酵素反応

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.

通过鉴定链霉菌的基因簇，发现了修饰聚酮化合物的新酶，该基因簇产生预期作为骨质疏松症治疗药物候选物的瑞维霉素A。在该基因簇中，发现了催化将琥珀酰基转移至叔醇的生物合成反应的酶。研究表明，该酶在生理环境下可进行困难的有机合成反应。本研究的目的是通过X射线晶体结构分析来阐明该酶的反应机制的细节。通过结晶条件探索，得到酶晶体。并在同步加速器装置上进行衍射实验，获得了分辨率达到1.8 A的衍射数据。通过对获得的数据进行结构分析的进展，预计未来酶的结构细节将变得清晰，反应机理将得到阐明。