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Protein conformer selection by ligand binding observed with crystallography
Author(s) -
Cao Yi,
Musah Rabi A.,
Wilcox Sheri K.,
Goodin David B.,
McRee Duncan E.
Publication year - 1998
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560070107
Subject(s) - conformational isomerism , chemistry , ligand (biochemistry) , crystallography , protein structure , kinetics , conformational change , stereochemistry , biochemistry , receptor , molecule , physics , organic chemistry , quantum mechanics
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.