Comparison of the substrate-binding pockets of the Rous sarcoma virus and human immunodeficiency virus type 1 proteases.
A steady state kinetic analysis of the avian myeloblastosis virus/Rous sarcoma virus (AMV/RSV) and human immunodeficiency virus Type 1 (HIV-1) retroviral proteases (PRs) was carried out using a series of 40 peptide substrates that are derivatives of the AMV/RSV nucleocapsid-PR cleavage site. These peptides contain single amino acid substitutions in each of the seven positions of the minimum length substrate required by the PR for specific and efficient cleavage. These peptide substrates are distinguished by the individual enzyme subsites of the AMV/RSV and HIV-1 PRs. The molecular basis for similarities and differences of the individual subsites for both proteases is discussed using steady state kinetic data and modeling based on crystal structures.
Cameron
C E
CE
Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4935.
Grinde
B
B
Jacques
P
P
Jentoft
J
J
Leis
J
J
Wlodawer
A
A
Weber
I T
IT
D000595:Amino Acid Sequence; D009189:Avian Myeloblastosis Virus / Q000201:enzymology*; D001358:Avian Sarcoma Viruses / Q000201:enzymology*; D001665:Binding Sites; D010450:Endopeptidases / Q000378:metabolism*; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
D010455:Peptides; D011994:Recombinant Proteins; D010450:Endopeptidases; D016333:HIV Protease