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The Conformation of a Peptidyl Methyl Ketone Inhibitor Bound to the Human Cytomegalovirus Protease
Author(s) -
LaPlante Steven R.,
Cameron Dale R.,
Aubry Norman,
Bonneau Pierre R.,
Déziel Robert,
GrandMaître Chantal,
Ogilvie William W.,
Kawai Stephen H.
Publication year - 1998
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/(sici)1521-3773(19981016)37:19<2729::aid-anie2729>3.0.co;2-4
Subject(s) - ketone , enzyme , chemistry , stereochemistry , protease inhibitor (pharmacology) , enzyme inhibitor , protease , biochemistry , biology , virology , organic chemistry , virus , viral load , antiretroviral therapy
A weak inhibitor means faster exchange! Since the methyl ketone MK2 is a weak noncovalent peptidyl inhibitor of the human cytomegalovirus protease, exchange between the free and enzyme‐bound forms is rapid. This allows for the use of transferred NOE NMR methods and molecular modeling, which show that the bound conformation of MK2 is an extended peptide. This is confirmed by the results of an X‐ray crystallographic analysis of a related enzyme–inhibitor complex.