1g35: Difference between revisions
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[[Image:1g35.gif|left|200px]] | [[Image:1g35.gif|left|200px]] | ||
'''CRYSTAL STRUCTURE OF HIV-1 PROTEASE IN COMPLEX WITH INHIBITOR, AHA024''' | {{Structure | ||
|PDB= 1g35 |SIZE=350|CAPTION= <scene name='initialview01'>1g35</scene>, resolution 1.8Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=AHF:2-[4-(HYDROXY-METHOXY-METHYL)-BENZYL]-7-(4-HYDROXYMETHYL-BENZYL)-1,1-DIOXO-3,6-BIS-PHENOXYMETHYL-1LAMBDA6-[1,2,7]THIADIAZEPANE-4,5-DIOL'>AHF</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= | |||
}} | |||
'''CRYSTAL STRUCTURE OF HIV-1 PROTEASE IN COMPLEX WITH INHIBITOR, AHA024''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1G35 is a [ | 1G35 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=1G35 OCA]. | ||
==Reference== | ==Reference== | ||
Synthesis and comparative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors., Schaal W, Karlsson A, Ahlsen G, Lindberg J, Andersson HO, Danielson UH, Classon B, Unge T, Samuelsson B, Hulten J, Hallberg A, Karlen A, J Med Chem. 2001 Jan 18;44(2):155-69. PMID:[http:// | Synthesis and comparative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors., Schaal W, Karlsson A, Ahlsen G, Lindberg J, Andersson HO, Danielson UH, Classon B, Unge T, Samuelsson B, Hulten J, Hallberg A, Karlen A, J Med Chem. 2001 Jan 18;44(2):155-69. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11170625 11170625] | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
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[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
''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 11:17:31 2008'' | ||
Revision as of 12:17, 20 March 2008
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| , resolution 1.8Å | |||||||
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| Ligands: | |||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HIV-1 PROTEASE IN COMPLEX WITH INHIBITOR, AHA024
OverviewOverview
We have previously reported on the unexpected flipped conformation in the cyclic sulfamide class of inhibitors. An attempt to induce a symmetric binding conformation by introducing P2/P2' substituents foreseen to bind preferentially in the S2/S2' subsite was unsuccessful. On the basis of the flipped conformation we anticipated that nonsymmetric sulfamide inhibitors, with P2/P2' side chains modified individually for the S1' and S2 subsites, should be more potent than the corresponding symmetric analogues. To test this hypothesis, a set of 18 cyclic sulfamide inhibitors (11 nonsymmetric and 7 symmetric) with different P2/P2' substituents was prepared and evaluated in an enzyme assay. To rationalize the structure-activity relationship (SAR) and enable the alignment of the nonsymmetric inhibitors, i.e., which of the P2/P2' substituents of the nonsymmetric inhibitors interact with which subsite, a CoMFA study was performed. The CoMFA model, constructed from the 18 inhibitors in this study along with seven inhibitors from previous work by our group, has successfully been used to rationalize the SAR of the cyclic sulfamide inhibitors. Furthermore, from the information presented herein, the SAR of the cyclic sulfamide class of inhibitors seems to differ from the SAR of the related cyclic urea inhibitors reported by DuPont and DuPont-Merck.
About this StructureAbout this Structure
1G35 is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
Synthesis and comparative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors., Schaal W, Karlsson A, Ahlsen G, Lindberg J, Andersson HO, Danielson UH, Classon B, Unge T, Samuelsson B, Hulten J, Hallberg A, Karlen A, J Med Chem. 2001 Jan 18;44(2):155-69. PMID:11170625
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