title: Reprint of "Crystal structure of chemically synthesized HIV-1 protease and a ketomethylene isostere inhibitor based on the p2/NC cleavage site" [Bioorg. Med. Chem. Lett. 18 (2008) 4554-4557].
abstract: Here we report the X-ray structures of chemically synthesized HIV-1 protease and the inactive [D25N]HIV-1 protease complexed with the ketomethylene isostere inhibitor Ac-Thr-Ile-Nlepsi[CO-CH(2)]Nle-Gln-Arg.amide at 1.4 and 1.8A resolution, respectively. In complex with the active enzyme, the keto-group was found to be converted into the hydrated gem-diol, while the structure of the complex with the inactive D25N enzyme revealed an intact keto-group. These data support the general acid-general base mechanism for HIV-1 protease catalysis.
authors.affiliation: Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. torbeev@uchicago.edu
authors.forename: Vladimir Yu
authors.initials: VY
authors.lastname: Torbeev
authors.forename: Kalyaneswar
authors.initials: K
authors.lastname: Mandal
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Terechko
authors.forename: Stephen B H
authors.initials: SB
authors.lastname: Kent