Dipartimento di Chimica and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centro d'Eccellenza MURST, Universita' della Calabria, I-87030 Arcavacata di Rende (CS), Italy.
J Am Chem Soc. 2009 Oct 21;131(41):14804-11. doi: 10.1021/ja9037142.
The possible mechanism by which the insulin-degrading enzyme (IDE) zinc-binding protease carries out its catalytic function toward two peptides of different length, simulating a portion of B chain of insulin, was investigated on an enzymatic model consisting of 130 /159 atoms, using the density functional theory method and the hybrid exchange-correlation functional B3LYP in gas phase and in the protein environment. Based on the geometry and relative stabilities of minima and transition states on the potential energy profiles, we determined that proteolysis reaction is exothermic and proceeds quickly as the barrier in the rate-limiting step falls widely within the range of values expected for an enzymatic catalysis, both in vacuum and in protein medium.
用密度泛函理论方法和混合交换相关泛函 B3LYP 在气相和蛋白质环境中，对由 130/159 个原子组成的酶模型，研究了胰岛素降解酶（IDE）锌结合蛋白酶对两种不同长度的肽（模拟胰岛素 B 链的一部分）进行催化作用的可能机制。根据势能曲线上的最小势能和过渡态的几何形状和相对稳定性，我们确定蛋白水解反应是放热的，并且快速进行，因为在限制步骤中的势垒广泛地处于酶催化作用的预期值范围内，无论是在真空中还是在蛋白质介质中。
