Analysis of subsite preferences of HIV-1 proteinase using MA/CA junction peptides substituted at the P3-P1' positions.
The residues P3, P2, P1, and P1' of a peptide corresponding to the matrix/capsid protein junction in the HIV-1 gag protein (Ser-Gln-Asn-Tyr-Pro-Ile-Val) were systematically replaced and the effect of these single amino acid substitutions on the hydrolysis of each peptide by HIV-1 proteinase was studied. Subsites S1 and S1' of the enzyme showed explicit preference for hydrophobic moieties, but beta-branched amino acids and proline are not tolerated in S1. The S2 subsite shows a preference for small polar and apolar amino acids; it may be occupied by Asn, Asp, Glu, Cys, Ala, or Val, other substitutions, especially by Gln and Ser, prevent hydrolysis of the peptides. In subsite S3 all amino acids except proline can be accommodated.
Billich
A
A
Department of Antiretroviral Therapy, Sandoz-Research Institute, Vienna, Austria.
Winkler
G
G
D000595:Amino Acid Sequence; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry; D015683:Gene Products, gag / Q000737:chemistry; D016333:HIV Protease / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D011498:Protein Precursors / Q000737:chemistry; D013379:Substrate Specificity; D014763:Viral Matrix Proteins / Q000737:chemistry
D015683:Gene Products, gag; D009842:Oligopeptides; D011498:Protein Precursors; D014763:Viral Matrix Proteins; D016333:HIV Protease