Journal Article
Proceedings of the National Academy of Sciences, vol. 111, iss. 28, pp. 10203-10208, 2014
Authors
Carlo Camilloni, Aleksandr B. Sahakyan, Michael J. Holliday, Nancy G. Isern, Fengli Zhang, Elan Z. Eisenmesser, Michele Vendruscolo
Abstract
Significance
One of the most widespread molecular switches in biochemical pathways is based on the isomerization of the amino acid proline, a process that normally is facilitated by enzymes known as “proline isomerases.” We show that cyclophilin A, one of the most common proline isomerases, acts by a simple mechanism, which we describe as an “electrostatic handle.” In this mechanism, the enzyme creates an electrostatic environment in its catalytic site that rotates a peptide bond in the substrate by pulling the electric dipole associated with the carbonyl group preceding the peptide bond itself. Our results thus identify a specific mechanism by which electrostatics is exploited in enzyme catalysis.
