title: Conformational selectivity of HIV-1 protease cleavage of X-Pro peptide bonds and its implications.
abstract: Kinetic measurements on a fluorescent peptide analog of the p17/p24 cleavage site of the Gag polyprotein demonstrate the conformational selectivity of human immunodeficiency virus, type 1 protease for the trans conformation of the Tyr-Pro bond. A mean cis/trans ratio of 0. 3, and a cis --> trans isomerization rate constant of 0.022 s-1 are determined at T = 22 degrees C. This rate is in excellent agreement with that predicted by 19F NMR studies of structurally analogous peptides containing a fluorine/hydroxyl substitution on the tyrosyl residue. Addition of recombinant human cyclophilin resulted in a significant enhancement of this rate, and it is proposed that this enzyme, which has been shown to be associated with the Gag protein, functions as an auxiliary enzyme for the protease during cleavage in the virion.
authors.affiliation: Laboratory of Structural Biology, NIEHS, Research Triangle Park, North Carolina 27709, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Vance
authors.forename: D A
authors.initials: DA
authors.lastname: LeBlanc
authors.forename: P
authors.initials: P
authors.lastname: Wingfield
authors.forename: R E
authors.initials: RE
authors.lastname: London
mesh_terms: D000591:Amino Acid Isomerases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D016384:Consensus Sequence; D015683:Gene Products, gag / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D019696:Peptidylprolyl Isomerase; D011392:Proline / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014443:Tyrosine
chemical_list: D002352:Carrier Proteins; D015683:Gene Products, gag; D011994:Recombinant Proteins; D014443:Tyrosine; D011392:Proline; D016333:HIV Protease; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase