The Conformation of a Peptidyl Methyl Ketone Inhibitor Bound to the Human Cytomegalovirus Protease

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.