1PRO
HIV-1 PROTEASE DIMER COMPLEXED WITH A-98881
Summary for 1PRO
| Entry DOI | 10.2210/pdb1pro/pdb |
| Descriptor | HIV-1 PROTEASE, (5R,6R)-2,4-BIS-(4-HYDROXY-3-METHOXYBENZYL)-1,5-DIBENZYL-3-OXO-6-HYDROXY-1,2,4-TRIAZACYCLOHEPTANE (3 entities in total) |
| Functional Keywords | aids, polyprotein, hydrolase, aspartic protease, endonuclease, rna-directed dna polymerase, hydrolase (aspartic protease) |
| Biological source | Human immunodeficiency virus 1 |
| Cellular location | Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P12499 |
| Total number of polymer chains | 2 |
| Total formula weight | 22245.24 |
| Authors | Park, C.H.,Kong, X.P.,Dealwis, C.G. (deposition date: 1995-07-18, release date: 1996-08-17, Last modification date: 2024-02-14) |
| Primary citation | Sham, H.L.,Zhao, C.,Stewart, K.D.,Betebenner, D.A.,Lin, S.,Park, C.H.,Kong, X.P.,Rosenbrook Jr., W.,Herrin, T.,Madigan, D.,Vasavanonda, S.,Lyons, N.,Molla, A.,Saldivar, A.,Marsh, K.C.,McDonald, E.,Wideburg, N.E.,Denissen, J.F.,Robins, T.,Kempf, D.J.,Plattner, J.J.,Norbeck, D.W. A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease. J.Med.Chem., 39:392-397, 1996 Cited by PubMed Abstract: The design, synthesis, and molecular modeling studies of a novel series of azacyclic ureas, which are inhibitors of human immunodeficiency virus type 1 (HIV-1) protease that incorporate different ligands for the S1', S2, and S2' substrate-binding sites of HIV-1 protease are described. The synthesis of this series is highly flexible in the sense that the P1', P2, and P2' residues of the inhibitors can be changed independently. Molecular modeling studies on the phenyl ring of the P2 and P2' ligand suggested incorporation of hydrogen-bonding donor/acceptor groups at the 3' and 4-positions of the phenyl ring should increase binding potency. This led to the discovery of compound 7f (A-98881), which possesses high potency in the HIV-1 protease inhibition assay and the in vitro MT-4 cell culture assay (Ki = approximately 5 pM and EC50 = 0.002 microM). This compares well with the symmetrical cyclic urea 1 pioneered at DuPont Merck. PubMed: 8558507DOI: 10.1021/jm9507183 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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