title: Fast peptidyl cis-trans isomerization within the flexible Gly-rich flaps of HIV-1 protease.
abstract: The catalytic aspartyl protease of the HIV-1 virus is a homodimer with two flaps that control access to the active site and are known to be flexible. However, knowledge of the atomistic mechanism of the flexibility is lacking. We show that the Gly-Gly omega-bond in the glycine-rich flap tips undergoes fast cis-trans isomerization on the microsecond to millisecond time scale rather than in the usual seconds. Further study reveals that the unexpectedly fast isomerization is a direct consequence of the beta-hairpin loop structure of the flap tips, which appears to be counterintuitive. After loop formation of a linear peptide containing the Gly-Gly motif, the rate of isomerization is shown to increase by many orders of magnitude.
authors.affiliation: Howard Hughes Medical Institute, Center for Theoretical Biological Physics, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA. dhamelbe@mccammon.ucsd.edu
authors.forename: Donald
authors.initials: D
authors.lastname: Hamelberg
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D005998:Glycine / Q000737:chemistry*; D016333:HIV Protease / Q000737:chemistry*; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism
chemical_list: D010455:Peptides; D016333:HIV Protease; D005998:Glycine