The zinc inhibition mechanism of carboxypeptidase A (CPA) has been theoretically studied by both semiempirical quantum mechanical and Molecular Dynamics calculations. Zinc monohydroxide, zinc dihydroxide and zinc trihydroxide, solvated by two, one or zero water molecules, respectively, have been chosen as potential inhibitors. The inhibition mechanism takes place through the formation of a stabilizing hydroxide bridge between the inhibitory zinc ion of zinc monohydroxide and the catalytic zinc ion. This kind of structure has already been proposed by Larsen and Auld13from their experimental results. Once the bridge is formed within the CPA-zinc monohydroxide complex, the system is unable to evolve towards cleavage of the substrate peptide bond. © CNRS-Gauthier-Villars.
|Journal||New Journal of Chemistry|
|Publication status||Published - 1 Dec 1996|