title: Homology modeling and S(N)2 displacement reaction of fluoroacetate dehalogenase from Burkholderia sp. FA1.
abstract: Fluoroacetate dehalogenase (EC 3.8.1.3) catalyzes the dehalogenation of fluoroacetate and other haloacetates. In order to investigate the relation between the structure and the function, and understand the reaction mechanism of the enzyme, a 3D model of fluoroacetate dehalogenase FAc-DEX FA1 was built by homology-based modeling. The 3D model was optimized by unconstrained molecular dynamics simulation. Furthermore, the optimized 3D model was assessed by comparison of specific properties with two known protein structures. From the final 3D model, we find that the main residues involved in the active site in FAc-DEX FA1 were Phe34, Trp148, Tyr147, Tyr212, Asp104, and His271; especially Asp104 was the key nucleophilic residue in substrate binding. A reaction model including Asp104 and the substrate fluoroacetate was then constructed and used to characterize explicit enzymatic reactions. In order to further illustrate catalytic properties, the equilibrium geometries, energies, and frequencies of stationary points (reactants, products, and transition states) of the reaction model were calculated at the B3LYP/6-31G level of theory in both gas phase and solution. The results showed that the reaction in gas was dynamically more favorable than in solution.
authors.affiliation: Institute of Theoretical Chemistry, State Key Laboratory of Theoretical and Computational Chemistry, Jilin University, Changchun 130023, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ze-Sheng
authors.initials: ZS
authors.lastname: Li
authors.forename: Jia Yan
authors.initials: JY
authors.lastname: Wu
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Zheng
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019117:Burkholderia / Q000201:enzymology* / Q000235:genetics; D002384:Catalysis; D003198:Computer Simulation; D005463:Fluoroacetates / Q000737:chemistry / Q000378:metabolism; D006846:Hydrocarbons, Halogenated / Q000737:chemistry / Q000378:metabolism; D006867:Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D005463:Fluoroacetates; D006846:Hydrocarbons, Halogenated; D006867:Hydrolases; C023098:haloacetate dehalogenase