Predicting an Improvement of Secondary Catalytic Activity of Promiscuos Isochorismate Pyruvate Lyase by Computational Design

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• 作者：Sergio Martí ; Juan André ; s ; Vicent Moliner ; Estanislao Silla ; Iñ ; aki Tuñ ; ó ; n ; Juan Bertr&aacute ; n
• 刊名：Journal of the American Chemical Society
• 出版年：2008
• 出版时间：March 12, 2008
• 年：2008
• 卷：130
• 期：10
• 页码：2894 - 2895
• 全文大小：66K
• 年卷期：v.130,no.10(March 12, 2008)
• ISSN：1520-5126

文摘

Improvement of the secondary catalytic activity of promiscuous enzymes can be guided by computational protein engineering. This methodology has been applied to isochorismate pyruvate lyase (IPL) that catalyzes isochorismate transformation into pyruvate and salicylate but it also presents secondary activity catalyzing the transformation of chorismate into prephenate. According to the computational results, a mutation of Val by Ile at position 38 would keep the enol pyruvyl moiety of the substrate in a diaxial conformation, closer to the TS geometry, thus reducing the free energy barrier of the chemical reaction 4.4 kcal·mol^-1 with respect to the native IPL.