Valence Bond and Enzyme Catalysis: A Time To Break Down and a Time To Build Up. Issue 19 (24th March 2015)

• Record Type: Journal Article
• Authors: Sharir‐Ivry, Avital; Varatharaj, Rajapandian; Shurki, Avital
• Is Part Of: Chemistry. Volume 21:Issue 19(2015)
• Page Start: 7159
• Page End: 7169
• Publication Date: 2015-03-24
• Subjects: computational chemistry -- enzyme catalysis -- enzyme design -- quantum mechanics -- valence bond theory; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201406236
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Understanding enzyme catalysis and developing ability to control of it are two great challenges in biochemistry. A few successful examples of computational‐based enzyme design have proved the fantastic potential of computational approaches in this field, however, relatively modest rate enhancements have been reported and the further development of complementary methods is still required. Herein we propose a conceptually simple scheme to identify the specific role that each residue plays in catalysis. The scheme is based on a breakdown of the total catalytic effect into contributions of individual protein residues, which are further decomposed into chemically interpretable components by using valence bond theory. The scheme is shown to shed light on the origin of catalysis in wild‐type haloalkane dehalogenase (wt‐DhlA) and its mutants. Furthermore, the understanding gained through our scheme is shown to have great potential in facilitating the selection of non‐optimal sites for catalysis and suggesting effective mutations to enhance the enzymatic rate. Abstract : VB thinks simple: Understanding enzyme catalysis and controlling it remain a great challenge. A valence‐bond‐based analysis is proposed that identifies the specific role played by each residue in the enzymatic reaction. The analysis provides a simple framework for a better understanding of enzyme catalysis and allows the selection of non‐optimal sites for catalysis as well as suggesting effective mutations to enhance the enzymatic rate.