Some of Antonio Ruzzini’s PhD thesis work has been selected to be highlighted on Biochemistry’s website.
http://pubs.acs.org/journals/bichaw/index.html
“A substrate-assisted mechanism of nucleophile activation in a Ser-His-Asp containing C-C bond hydrolase.”
Author(s): Ruzzini, Antonio; Bhowmik,Shiva; Ghosh, Subhangi; Yam, Katherine; Bolin, Jeffrey; Eltis, Lindsay
Published in American Chemical Society Journal Biochemistry. Biochemistry. 2013 52:7428-38.
Summary
Meta-Cleavage product (MCP) hydrolases are involved in the bacterial degradation of aromatic compounds and steroids: one homolog is a determinant in the degradation of PCBs (polychlorinated biphenyls) while another is a potential target for novel therapeutics to treat TB. These enzymes utilize a Ser-His-Asp triad to catalyze the unusual hydrolysis of a carbon-carbon bond. In this study, we used kinetic, mutagenesis and structural approaches to demonstrate that the substrate plays a role in activating the catalytic serine for subsequent nucleophilic attack. This substrate-assisted mechanism of nucleophilic catalysis distinguishes MCP hydrolases from other serine hydrolases, and highlights the versatility of the catalytic triad.