DFT Study on the Roles of Calcium and Its Coordination Variation Play in the Mechanism of Diisopropyl Fluorophosphatase
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- 英文论文题名：DFT Study on the Roles of Calcium and Its Coordination Variation Play in the Mechanism of Diisopropyl Fluorophosphatase
- 论文作者：Ling Yang ; W.Tian ; R.-Z.Liao
- 英文论文作者：Ling Yang ; W.Tian ; R.-Z.Liao ; Institute of Theoretical and Simulation Chemistry ; School of Chemistry and Chemical Engineering ; Harbin Institute of Technology ; School of Chemistry and Chemical Engineering ; Huazhong University of Science and Technology
- 年：2016
- 作者机构：Institute of Theoretical and Simulation Chemistry, School of Chemistry and Chemical Engineering, Harbin Institute of Technology;School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology;
- 英文论文关键词：Enzymatic reaction ; Hydrolysis Mechanism ; Density functional calculations
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第十九分会：化学中的量子与经典动力学
- 语种：英文
- 分类号：O643.3;O641.4
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第十九分会 ; 化学中的量子与经典动力学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：33k
- 原文格式：D
- 会议级别：全国
摘要
Catalytic mechanism of diisopropyl fluorophosphatase from Loligo vulgaris is investigated using the hybrid density functional theory method B3LYP with a large quantum chemical model of the active site. For the first step, both Asp229 and an activated water molecule are capable of proceeding in-line attack on the substrate with the associated barriers 14.8 and 6.0 kcal/mol, respectively. Asp229 plays a dual role during the two reaction processes as either a nucleophile or a general base to activate H_2O. From the phosphoenzyme intermediate with hexa-coordinated Ca~(2+), the uncoordinated Glu21 activated an additional H_2O to attack the carbon center of Asp229 and make the phosphate release. Asn120 and Asn175 promote the elimination of the fluoride via donating strong hydrogen bonds. Coordination variation of calcium plays important role of the enzymatic reaction to occur. The calculated detailed reaction mechanisms will promote the structure-based protein engineering to modify hydrolysis rates and substrate specific.
Catalytic mechanism of diisopropyl fluorophosphatase from Loligo vulgaris is investigated using the hybrid density functional theory method B3LYP with a large quantum chemical model of the active site. For the first step, both Asp229 and an activated water molecule are capable of proceeding in-line attack on the substrate with the associated barriers 14.8 and 6.0 kcal/mol, respectively. Asp229 plays a dual role during the two reaction processes as either a nucleophile or a general base to activate H_2O. From the phosphoenzyme intermediate with hexa-coordinated Ca~(2+), the uncoordinated Glu21 activated an additional H_2O to attack the carbon center of Asp229 and make the phosphate release. Asn120 and Asn175 promote the elimination of the fluoride via donating strong hydrogen bonds. Coordination variation of calcium plays important role of the enzymatic reaction to occur. The calculated detailed reaction mechanisms will promote the structure-based protein engineering to modify hydrolysis rates and substrate specific.
Catalytic mechanism of diisopropyl fluorophosphatase from Loligo vulgaris is investigated using the hybrid density functional theory method B3LYP with a large quantum chemical model of the active site. For the first step, both Asp229 and an activated water molecule are capable of proceeding in-line attack on the substrate with the associated barriers 14.8 and 6.0 kcal/mol, respectively. Asp229 plays a dual role during the two reaction processes as either a nucleophile or a general base to activate H_2O. From the phosphoenzyme intermediate with hexa-coordinated Ca~(2+), the uncoordinated Glu21 activated an additional H_2O to attack the carbon center of Asp229 and make the phosphate release. Asn120 and Asn175 promote the elimination of the fluoride via donating strong hydrogen bonds. Coordination variation of calcium plays important role of the enzymatic reaction to occur. The calculated detailed reaction mechanisms will promote the structure-based protein engineering to modify hydrolysis rates and substrate specific.
引文
[1]Blum,M.M.;L?hr,F.;Richardt,A.;Rüterjans,H.;Chen,J.C.H.J.Am.Chem.Soc.2006,128:12750.
[2]Yang,Y.C.;Baker,J.A.;Ward,J.R.Chem.Rev.1992,92:1729.
[3]Scharff,E.I.;Koepke,J.;Fritzsch,G.;Lucke,C.;Ruterjans,H.Structure 2001,9:493.
[2]Yang,Y.C.;Baker,J.A.;Ward,J.R.Chem.Rev.1992,92:1729.
[3]Scharff,E.I.;Koepke,J.;Fritzsch,G.;Lucke,C.;Ruterjans,H.Structure 2001,9:493.