Modulation of the rate, enantioselectivity, and substrate specificity of semisynthetic transaminases based on lipid binding proteins using site directed mutagenesis

被引：22

作者：

Kuang, H ^{[1
]}

Davies, RR ^{[1
]}

Distefano, MD ^{[1
]}

机构：

[1] UNIV MINNESOTA,DEPT CHEM,MINNEAPOLIS,MN 55455

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 15期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1016/S0960-894X(97)00358-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Fatty acid binding proteins are a class of small 15 kDa proteins with a simple architecture that forms a large solvent sequestered cavity. In previous work, pie demonstrated that reductive amination reactions could be performed in this cavity by covalent attachment of a pyridoxamine cofactor to the protein. Here, we report the results of experiments in which the position of pyridoxamine attachment has been varied by site directed mutagenesis. The conjugate IFABP-PX60 reacts at least 9.4-fold more rapidly than our original conjugate ALBP-PX, while IFABP-PX72 inverts the enantioselectivity of reactions (compared to ALBP-PX) and LFABP-PX104 displays very selective substrate specificty. These results indicate that site-directed mutagenesis can be used to tune the rate, enantioselectivity, and substrate specificity of semisynthetic transaminases based on fatty acid binding proteins. (C) 1997 Elsevier Science Ltd.

引用

页码：2055 / 2060

页数：6

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