Yamamoto D, Shiota N, Takai S, Ishida T, Okunishi H, Miyazaki M
Medical Computation Center, Osaka Medical College, Japan.
Biochem Biophys Res Commun. 1998 Jan 6;242(1):158-63. doi: 10.1006/bbrc.1997.7875.
Although angiotensin (ANG)-I is a substrate sensitive to chymase, the cleavage site differs among the chymase families. While human chymase (HC) hydrolyses the Phe8-His9 bond of ANG-I to ANG-II, rat chymase (RMCP-I) degrades the Tyr4-Ile5 bond of ANG-I to the inactive fragments. To clarify this different catalysis for ANG-I at the atomic level, three-dimensional structures of HC and RMCP-I were constructed by the molecular dynamic simulation. The energy-refined models clearly showed the significant difference in the electrostatic potential of the solvent surface. From the modeling study of their complex structures with ANG-I, the functional difference between both enzymes was clearly related with the electrostatic difference, especially at the C-terminal substrate-binding site.
尽管血管紧张素（ANG）-I是糜酶敏感的底物，但糜酶家族之间的切割位点有所不同。人糜酶（HC）将ANG-I的Phe8-His9键水解为ANG-II，而大鼠糜酶（RMCP-I）则将ANG-I的Tyr4-Ile5键降解为无活性片段。为了在原子水平上阐明对ANG-I的这种不同催化作用，通过分子动力学模拟构建了HC和RMCP-I的三维结构。能量优化模型清楚地显示了溶剂表面静电势的显著差异。从它们与ANG-I的复合结构的建模研究来看，两种酶之间的功能差异明显与静电差异有关，特别是在C端底物结合位点。
