Protein Science, Vol 7, Issue 1 72-78, Copyright © 1998 by Cold Spring Harbor Laboratory Press

ARTICLE

Protein conformer selection by ligand binding observed with crystallography

Y. CAO, R. A. MUSAH, S. K. WILCOX, D. B. GOODIN and D. E. MCREE
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037

A large-scale movement between ``closed'' and ``open'' conformations of a protein loop was observed directly with protein crystallography by trapping individual conformers through binding of an exogenous ligand and characterization with solution kinetics. The buried indole ring of Trp(191) in cytochrome c peroxidase (CCP) was displaced by exogenous ligands, causing a conformational change of loop Pro(190)-Asn(195) and exposing Trp(191) to the protein surface. Kinetic measurements are consistent with a two-step binding mechanism in which the rate-limiting step is a transition of the protein to the open state, which then binds the ligand. This large-scale conformational change of a functionally important region of CCP is independent of ligand and indicates that about 4% of the wild-type protein is in the open form in solution at any given time.
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