Use of steady state kinetic methods to elucidate the kinetic and chemical mechanisms of retroviral proteases.
Despite the current plethora of structural data of HIV-1 protease and the availability of potent inhibitors, whose structures are based in part on the presumed mechanism of action of this enzyme, our actual understanding of its chemical mechanism has been until now based largely on the precedents of the mammalian and fungal aspartic proteases and static three-dimensional data. The available steady state kinetic data of the protease, as reviewed here, constitute a first step in a detailed description of the mechanism of the enzyme to complement the structural data.
Department of Cardiovascular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08540.
T D
TD
Meek
E J
EJ
Rodriguez
T S
TS
Angeles
D000595:Amino Acid Sequence; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods; D002863:Chromogenic Compounds; D003124:Colorimetry / Q000379:methods; D003903:Deuterium / Q000378:metabolism; D005470:Fluorometry / Q000379:methods; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes; D010103:Oxygen Isotopes; D010446:Peptide Fragments / Q000032:analysis; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011874:Radiometry / Q000379:methods
D002863:Chromogenic Compounds; D017320:HIV Protease Inhibitors; D009587:Nitrogen Isotopes; D010103:Oxygen Isotopes; D010446:Peptide Fragments; D010455:Peptides; D003903:Deuterium; D016333:HIV Protease