COMPUTER-SIMULATION OF THE INITIAL PROTON-TRANSFER STEP IN HUMAN CARBONIC ANHYDRASE-I

被引：114

作者：

AQVIST, J ^{[1
]}

WARSHEL, A ^{[1
]}

机构：

[1] UNIV SO CALIF,DEPT CHEM,LOS ANGELES,CA 90089

来源：

JOURNAL OF MOLECULAR BIOLOGY | 1992年 / 224卷 / 01期

关键词：

FREE ENERGY CALCULATIONS; FREE ENERGY PROFILES; CARBONIC ANHYDRASE; PROTON TRANSFER; ENZYME MECHANISM;

D O I：

10.1016/0022-2836(92)90572-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The initial water proteolysis step in the proton transfer "half-reaction" of human carbonic anhydrase I is simulated using the empirical valence bond method in combination with free energy perturbation molecular dynamics calculations. A free energy profile for the enzyme catalysed reaction and the corresponding pKa associated with ionization of the zinc-bound water is calculated. The obtained pKa value of 7 to 8 appears to be in good agreement with experimental observations and the calculated rate constant for this step is also compatible with kinetic data. The simulations clearly emphasize the important electrostatic effect associated with the catalytic zinc ion. © 1992.

引用

页码：7 / 14

页数：8

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