The University of Texas at El Paso

The University of Texas at El Paso
Chemistry Department
“Structural and Functional Models of Nitrile
Hydratase: A Smart Way to Hydrolyze Nitriles”
Pradip K. Mascharak, Ph.D.
Dept of Chemistry & Biochemistry
University of California, Santa Cruz
Microbial assimilation of organic nitriles is catalyzed by the enzyme nitrile
hydratase. This enzyme contains at its active site a low-spin non-heme Fe(III) or a
non-corrinoid Co(III) metal center.
The M(III) center is ligated to two
deprotonated carboxamido nitrogens from the peptide backbone (quite unusual!)
and three cysteine sulfurs located in a highly conserved –C-S-L-C-S-C- motif. Two
of the three thiolato sulfurs are further modified to Cys-sulfenic and Cys-sulfinic
acid moieties (quite unusual!) to provide a unique metal site that promote rapid
hydration of nitriles to the corresponding amides. We have established the
mechanism of nitrile hydration via a “synthetic analogue approach”. In such
research, we have synthesized smaller mimics of the active site and studied their
spectroscopic and redox properties to determine the roles of the various donor
atoms in the unprecedented coordination sphere of the M(III) metal centers. These
small mimics or “chemozymes” serve as efficient biomimetic catalysts for the nitrilecarboxamide transformation. These results along with new insights into the roles of
modified peptide residues on the reactivity of metal centers will be discussed.
Friday, April 22, 2005
4:00 p.m.
PSCI Room 208