1984, Ph.D. in Chemical Physics, University of Minnesota, Minneapolis
1979, B.S. in Chemistry, Royal Holloway College, London University
Hydrogen bonds to metal–ligands in proteins play a vital role in biological function. They help to stabilize/protect the metal complex and enhance metal-binding affinity/specificity, enzyme–substrate recognition, and enzyme activation. Yet, knowledge of the preferred hydrogen-bonding partners of metal ligands in different metalloproteins is lacking. Using well-calibrated methods, we have determined the preferred hydrogen-bonding partners of Cys– bound to native Zn2+ or xenobiotic Cd2+ in Zn-fingers of varying net charge and solvent accessibility as well as the key factors underlying the observed preference. We show how secondary hydrogen-bonding interactions with metal-bound thiolates might exert a significant impact on Zn2+→Cd2+ substitution and thus protein function. Knowing which Zn-fingers may be vulnerable to structural deformation by Cd2+ is important since this would lead to their inactivation, which might impair cell growth, differentiation, cell-cycle control, and DNA repair.