期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 15, 期 30, 页码 7394-7403出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.200801813
关键词
ab initio calculations; density functional calculations; fluoroacetate dehalogenase; reaction mechanisms
资金
- Japan Society for the Promotion of Science (JSPS) [18750048, 18350088, 18GS0207, 19066013]
- Ministry of Culture, Sports. Science and Technology of Japan (MEXT)
- Nanotechnology Support Project of MEXT
- Joint Project of Chemical Synthesis Core Research Institutions of MEXT and CREST of Japan Science and Technology
The biological dehalogenation of fluoroacetate carried out by fluoroacetate dehalogenase is discussed by using quantum mechanical/molecular mechanical (OM/MM) calculations for a whole-enzyme model of 10800 atoms. Substrate fluoroacetate is anchored by a hydrogen-bonding network with water molecules and the surrounding, amino acid residues of Arg105, Arg108, His149, Trp150, and Tyr212 in the active site in a similar Way to haloalkane dehalogenase. Asp104 is likely to act as a nucleophile to attack the alpha-carbon of fluoroacetate, resulting in the formation of an ester intermediate, which is subsequently hydrolyzed by the nucleophilic attack of a water molecule to the carbonyl carbon atom. The cleavage of the strong C-F bond is greatly facilitated by the hydrogen-bonding interactions between the leaving fluorine atom and the three amino acid residues of His149, Trp150, and Tyr212. The hydrolysis of the ester intermediate is initiated by a proton transfer from the water molecule to His271 and by the simultaneous nucleophilic attack of the water molecule. The transition state and produced tetrahedral intermediate Lire stabilized by Asp128 and the oxy-anion hole composed of Phe34 and Arg105.
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