Premium
HIV protease substrate conformation: modulation by cyclophilin A
Author(s) -
McCornack Melissa A,
Kakalis Lazaros T,
Caserta Carlo,
Handschumacher Robert E,
Armitage Ian M
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00974-5
Subject(s) - cyclophilin a , cyclophilin , protease , hiv 1 protease , human immunodeficiency virus (hiv) , substrate (aquarium) , biophysics , modulation (music) , chemistry , microbiology and biotechnology , biochemistry , biology , virology , enzyme , physics , ecology , gene , acoustics
Cyclophilin A (CyPA), a cytosolic peptidyl‐prolyl trans‐cis isomerase can accelerate the trans‐cis isomerization of Xxx‐Pro peptide bonds. One‐ and two‐dimensional 1 H‐NMR spectroscopy were used to determine that the heptapeptide Ser‐Gln‐Asn‐Tyr‐Pro‐Ile‐Val, a model peptide of an HIV‐1 protease cleavage site in the gag polyprotein of HIV‐1, is a substrate for CyPA. Experiments revealed a slow exchange about the Tyr‐Pro peptide bond with 30±5% in the cis conformation (pH 1–9). While the interconversion rate is too slow to measure by kinetic NMR methods in the absence of CyPA, these methods, saturation transfer and NOE experiments, established that CyPA enhanced the rate of trans‐cis interconversion, a process inhibited by cyclosporin A (CsA). With a substrate:CyPA ratio of 40:1, an interconversion rate of 2.5 s −1 at 25°C was observed.