Gibney, Brian R.
Professor, Chemistry Department, Brooklyn College, The City University of New York
Degree(s) and awards
Ph.D. (Chemistry) The University of Michigan
The Gibney laboratory is focused on developing the nascent field of de novo metalloprotein design as a constructive methodology to delineate the fundamental engineering of metalloproteins, and to utilize their distinct chemistry for therapeutic use. Currently, we are delineating the role(s) of zinc ions in controlling gene expression in human cancer via the zinc finger proteins (ZFPs). Our investigative tools center on measuring the thermodynamics of metal-peptide and metal-protein equilibria. Our near-term goal is to provide the basis for improvements in the computational design of metalloproteins toward his long-term goal of designing synthetic metalloproteins of therapeutic value. Our studies reveal biochemical design principles that have advanced the field to the point where multi-cofactor metalloproteins like those involved in human cancer can be rationally designed and structurally characterized.
Zinc finger proteins are the largest class of metalloproteins in the human genome and their gene regulation function is fundamental to numerous human cancers. ZFPs exhibit metal-induced protein folding events, where the ZFP is unfolded in the absence of zinc and folds into its biologically active form upon zinc ion binding. The coupled nature of metal-ion binding and protein folding obscured the thermodynamics of each since their discovery in the 1980’s. Using a simple designed peptide with the classic ZFP coordination motifs, the Gibney laboratory was able to decouple the thermodynamics and show that the cost of protein folding free energy (+0-5 kcal/mol) is minimal compared to the free energy of Zn(II) binding, -15 kcal/mol. Current work is focused on the interaction of zinc with human transcription factor IIB and the Wilms Tumor Suppressor.
Grants over the last 5 years: No federal grant