15gag proteinase of myeloblastosis-associated virus: specificity studies with substrate-based inhibitors.
The specificity of the proteinase of myeloblastosis-associated virus (MAV) was studied with (a) 21 substrate-based inhibitors, (b) 9 inhibitors with pseudopalindrome sequences, (c) 8 chimeric inhibitors, and (d) 3 compounds designed as human immunodeficiency virus 1 (HIV-1) proteinase inhibitors. The central inhibitory unit (transition state or cleaved bond analog) and the role of the inhibitor side chains from P4 to P4' were investigated. MAV proteinase prefers an aromatic side chain in P1 and a small aliphatic nonpolar chain in P2 and P2'. Residues in P5 and P4 positions are outside of the short catalytic cleft of the enzyme, but still influence binding considerably. The data obtained provide evidence that the MAV proteinase has generally lower specificity and poorer binding than the HIV proteinase.
Pavlícková
L
L
Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Science, Prague.
Stys
D
D
Soucek
M
M
Urban
J
J
Hrusková
O
O
Sedlácek
J
J
Strop
P
P
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D009189:Avian Myeloblastosis Virus / Q000201:enzymology*; D016333:HIV Protease / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D009842:Oligopeptides; D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C036946:protease p15