Models for protein–zinc ion binding sites. II. The catalytic sites*

The first and selected members of the second coordination shells for four model protein–Zn(II) ion catalytic sites have been studied using ab initio computational methodology. The influence of deprotonation on the structure and relative energetics of model complexes was examined. Significant lengthening of the Zn(II)–S, Zn(II)–O, and Zn(II)–N ionic distance is observed as the negative charge about the Zn(II) ion increases. In a model Escheridia coli cytidine deaminase site, we find a substantial lengthening of the Zn–SH2 ionic distance in the active site, which corresponds to the lengthening found for transition state analogs in X-ray crystal structures. The lowest energy complex of a sulfur-containing ligand was found to be singly deprotonated, with the complex having an overall charge of +1. The deprotonation of any ligand in a model complex for thermolysin, on the other hand, was found to be endothermic. The influence of other ligands of the metal ion, along with second-shell ligands, on the energy requirement for deprotonation was also examined for other model systems. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 150–165, 2001