Ab Initio Determination of the Structure of the Active Site of a Metalloenzyme: Metal Substitution in Phospotriesterase using Density Functional Methods

Published

February 1, 1999

Author(s)

S A. Kafafi, Morris Krauss

Abstract

A number of previous studies have determined that a metalloenzyme active site is inherently determined by the ligands and metal and only weakly perturbed by the surrounding protein environment. This conclusion is now being tested for several families of bimetallic enzymes. Metal substitution is examined for phosphotriesterase (PTE) with all possible substitutions of zinc and cadmium in the two sites. A new density functional theory (DFT) functional is used in this study which has yielded accurate structures and thermochemistry for molecules made up of first and second row atoms. Comparisons between Hartee-Fock and DFT structures are in good agreement, suggesting this functional is useful in studying transition metal enzyme active sites. Good agreement between the x-ray and in vacuo optimized structures is also obtained for the Zn-Zn and Cd-Cd enzymes. This supports the analysis of the PTE active site as an inherent complex and suggests that accurate structures can be obtained for other metal substitutions for which no experimental structures are available. A unique zinc/cadmium hybrid was observed experimentally and the structure of this active site is theoretically predicted. The polarization of bound water at this very polar active site is very large, suggesting it is the reactive nucleophile.

Citation

International Journal of Quantum Chemistry

Volume

75

Pub Type

Journals

Keywords

cadmium enzyme, metalloenzyme active site, nucleophile, structure, zinc enzyme, zinc-cadmium enzyme

Citation

Kafafi, S. and Krauss, M. (1999), Ab Initio Determination of the Structure of the Active Site of a Metalloenzyme: Metal Substitution in Phospotriesterase using Density Functional Methods, International Journal of Quantum Chemistry (Accessed October 13, 2025)