The Important Role of Halogen Bond in Substrate Selectivity of Enzymatic Catalysis

• Published in: Scientific reports Vol. 6; no. 1; p. 34750
• Main Authors: Jiang, Shuiqin, Zhang, Lujia, Cui, Dongbin, Yao, Zhiqiang, Gao, Bei, Lin, Jinping, Wei, Dongzhi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.10.2016; Nature Publishing Group
• Subjects: 38/23; 38/77; 631/45/173; 639/638/77/603; 82/16; 82/80; Aminohydrolases - chemistry; Aminohydrolases - genetics; Aminohydrolases - metabolism; Biosynthesis; Catalysis; Catalytic Domain; Clinical trials; Conformation; Drug development; Drug Discovery; Halogens - chemistry; Humanities and Social Sciences; Models, Molecular; Molecular Conformation; Molecular Dynamics Simulation; Molecular Structure; multidisciplinary; Mutation; Nitrilase; Phenylacetates - chemistry; Phenylacetates - metabolism; Quantum Theory; Science; Substrate Specificity; Substrates
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep34750

The use of halogen bond is widespread in drug discovery, design, and clinical trials, but is overlooked in drug biosynthesis. Here, the role of halogen bond in the nitrilase-catalyzed synthesis of ortho-, meta-, and para-chlorophenylacetic acid was investigated. Different distributions of halogen bond induced changes of substrate binding conformation and affected substrate selectivity. By engineering the halogen interaction, the substrate selectivity of the enzyme changed, with the implication that halogen bond plays an important role in biosynthesis and should be used as an efficient and reliable tool in enzymatic drug synthesis.