3PHV

X-RAY ANALYSIS OF HIV-1 PROTEINASE AT 2.7 ANGSTROMS RESOLUTION CONFIRMS STRUCTURAL HOMOLOGY AMONG RETROVIRAL ENZYMES

Summary for 3PHV

• Entry DOI: 10.2210/pdb3phv/pdb
• Descriptor: UNLIGANDED HIV-1 PROTEASE (1 entity in total)
• Functional Keywords: hydrolase, aspartic proteinase
• Biological source: HIV-1 M:B_HXB2R
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585
• Total number of polymer chains: 1
• Total formula weight: 10803.76

Authors

Lapatto, R.,Blundell, T.L.,Hemmings, A.,Wilderspin, A.,Wood, S.P.,Danley, D.E.,Geoghegan, K.F.,Hawrylik, S.J.,Hobart, P.M. (deposition date: 1991-11-04, release date: 1992-01-15, Last modification date: 2024-02-21)

Primary citation

Lapatto, R.,Blundell, T.,Hemmings, A.,Overington, J.,Wilderspin, A.,Wood, S.,Merson, J.R.,Whittle, P.J.,Danley, D.E.,Geoghegan, K.F.,Hawrylik, S.J.,Lee, S.E.,Scheld, K.G.,Hobart, P.M.
X-ray analysis of HIV-1 proteinase at 2.7 A resolution confirms structural homology among retroviral enzymes.
Nature, 342:299-302, 1989

PubMed Abstract: Knowledge of the tertiary structure of the proteinase from human immunodeficiency virus HIV-1 is important to the design of inhibitors that might possess antiviral activity and thus be useful in the treatment of AIDS. The conserved Asp-Thr/Ser-Gly sequence in retroviral proteinases suggests that they exist as dimers similar to the ancestor proposed for the pepsins. Although this has been confirmed by X-ray analyses of Rous sarcoma virus and HIV-1 proteinases, these structures have overall folds that are similar to each other only where they are also similar to the pepsins. We now report a further X-ray analysis of a recombinant HIV-1 proteinase at 2.7 A resolution. The polypeptide chain adopts a fold in which the N- and C-terminal strands are organized together in a four-stranded beta-sheet. A helix precedes the single C-terminal strand, as in the Rous sarcoma virus proteinase and also in a synthetic HIV-1 proteinase, in which the cysteines have been replaced by alpha-aminobuytric acid. The structure reported here provides an explanation for the amino acid invariance amongst retroviral proteinases, but differs from that reported earlier in some residues that are candidates for substrate interactions at P3, and in the mode of intramolecular cleavage during processing of the polyprotein.

PubMed: 2682266
DOI: 10.1038/342299a0

Experimental method

X-RAY DIFFRACTION (2.7 Å)