1pro: Difference between revisions
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'''HIV-1 PROTEASE DIMER COMPLEXED WITH A-98881''' | {{Structure | ||
|PDB= 1pro |SIZE=350|CAPTION= <scene name='initialview01'>1pro</scene>, resolution 1.8Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=A88:(5R,6R)-2,4-BIS-(4-HYDROXY-3-METHOXYBENZYL)-1,5-DIBENZYL-3-OXO-6-HYDROXY-1,2,4-TRIAZACYCLOHEPTANE'>A88</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] | |||
|GENE= | |||
}} | |||
'''HIV-1 PROTEASE DIMER COMPLEXED WITH A-98881''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1PRO is a [ | 1PRO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PRO OCA]. | ||
==Reference== | ==Reference== | ||
A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease., Sham HL, Zhao C, Stewart KD, Betebenner DA, Lin S, Park CH, Kong XP, Rosenbrook W Jr, Herrin T, Madigan D, Vasavanonda S, Lyons N, Molla A, Saldivar A, Marsh KC, McDonald E, Wideburg NE, Denissen JF, Robins T, Kempf DJ, Plattner JJ, Norbeck DW, J Med Chem. 1996 Jan 19;39(2):392-7. PMID:[http:// | A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease., Sham HL, Zhao C, Stewart KD, Betebenner DA, Lin S, Park CH, Kong XP, Rosenbrook W Jr, Herrin T, Madigan D, Vasavanonda S, Lyons N, Molla A, Saldivar A, Marsh KC, McDonald E, Wideburg NE, Denissen JF, Robins T, Kempf DJ, Plattner JJ, Norbeck DW, J Med Chem. 1996 Jan 19;39(2):392-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8558507 8558507] | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
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[[Category: Park, C H.]] | [[Category: Park, C H.]] | ||
[[Category: A88]] | [[Category: A88]] | ||
[[Category: | [[Category: aid]] | ||
[[Category: aspartic protease]] | [[Category: aspartic protease]] | ||
[[Category: endonuclease]] | [[Category: endonuclease]] | ||
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[[Category: rna-directed dna polymerase]] | [[Category: rna-directed dna polymerase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:28:05 2008'' | ||
Revision as of 14:28, 20 March 2008
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| , resolution 1.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HIV-1 PROTEASE DIMER COMPLEXED WITH A-98881
OverviewOverview
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.
About this StructureAbout this Structure
1PRO is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease., Sham HL, Zhao C, Stewart KD, Betebenner DA, Lin S, Park CH, Kong XP, Rosenbrook W Jr, Herrin T, Madigan D, Vasavanonda S, Lyons N, Molla A, Saldivar A, Marsh KC, McDonald E, Wideburg NE, Denissen JF, Robins T, Kempf DJ, Plattner JJ, Norbeck DW, J Med Chem. 1996 Jan 19;39(2):392-7. PMID:8558507
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