Dr. Lim, Carmay 林小喬 博士



How First Shell–Second Shell Interactions and Metal Substitution Modulate Protein Function

Inorganic Chemistry, Jun 15, 2018

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.

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