title: The Important Role of Halogen Bond in Substrate Selectivity of Enzymatic Catalysis.
abstract: 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.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Shuiqin
authors.initials: S
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Lujia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Dongbin
authors.initials: D
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Wei
mesh_terms: D000619:Aminohydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002384:Catalysis; D020134:Catalytic Domain; D055808:Drug Discovery; D006219:Halogens / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009154:Mutation; D010648:Phenylacetates / Q000737:chemistry / Q000378:metabolism*; D011789:Quantum Theory; D013379:Substrate Specificity
chemical_list: D006219:Halogens; D010648:Phenylacetates; D000619:Aminohydrolases; C021867:nitrilase; C025136:phenylacetic acid