Modelling the active site of glyceraldehyde-3 phosphate dehydrogenase with the LSCF formalism |
| |
Authors: | Alain Cartier David Brown Bernard Maigret Sandrine Boschi-Muller Sophie Rahuel-Clermont Guy Branlant |
| |
Affiliation: | (1) Laboratoire de Chime Théorique, UMR CNRS-UHP 7565, Université Henri Poincaré-Nancy I, B.P. 239, F-54506 Vandoeuvre-lès-Nancy Cedex, France (Part of the Institut Nancéien de Chimie Moléculaire), FR;(2) UMR CNRS-UHP 7567, Université Henri Poincaré-Nancy I, B.P. 239, F-54506 Vandoeuvre-lès-Nancy Cedex, France, FR |
| |
Abstract: | In the framework of a theoretical approach to the relationship between structure and reactivity of the catalytic centers of enzymes, glyceraldehyde-3 phosphate dehydrogenase (GAPDH) has been chosen as a model enzyme. In GAPDH, the proximity of His176 increases the reactivity of Cys149 at neutral pH; however, its presence alone is not sufficient to explain the reactivity of the catalytic Cys. In order to determine which other interactions play an important role, a study of the geometric and electronic structure of the catalytic site has been made using a hybrid quantum mechanics/molecular mechanics local self-consistent field method. This allows the computation of the electronic properties of amino acid residues in subsystems influenced by other parts of the macromolecule. The quantum subsystem was centered on the Cys149 residue of GAPDH. The structures of GAPDH taken from the crystallographic database did not include hydrogen atoms and these had to be added taking into account the fact that, in the active site, His176 has three tautomeric forms: δ-His protonated, ε-His protonated and His+. The results presented here suggest that the most stable His…Cys system in GAPDH is a strongly hydrogen-bonded Cys149 −/His176 + ion pair. Received: 24 March 1998 / Accepted: 3 September 1998 / Published online: 23 November 1998 |
| |
Keywords: | : Enzymatic catalysis Glyceraldehyde-3 phosphate dehydrogenase Quantum mechanics/molecular mechanics methods |
本文献已被 SpringerLink 等数据库收录! |
|