3st5
From Proteopedia
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| - | [[ | + | ==Crystal structure of wild-type HIV-1 protease with C3-Substituted Hexahydrocyclopentafuranyl Urethane as P2-Ligand, GRL-0489A== |
| + | <StructureSection load='3st5' size='340' side='right' caption='[[3st5]], [[Resolution|resolution]] 1.45Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3st5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(bru_isolate) Human immunodeficiency virus type 1 (bru isolate)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ST5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ST5 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G89:(3R,3AR,5R,6AR)-3-HYDROXYHEXAHYDRO-2H-CYCLOPENTA[B]FURAN-5-YL+[(2S,3R)-3-HYDROXY-4-{[(4-METHOXYPHENYL)SULFONYL](2-METHYLPROPYL)AMINO}-1-PHENYLBUTAN-2-YL]CARBAMATE'>G89</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ien|2ien]], [[3dk1|3dk1]], [[2hb3|2hb3]], [[3h5b|3h5b]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11686 Human immunodeficiency virus type 1 (BRU ISOLATE)])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3st5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3st5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3st5 RCSB], [http://www.ebi.ac.uk/pdbsum/3st5 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report the design, synthesis, biological evaluation, and the X-ray crystal structure of a novel inhibitor bound to the HIV-1 protease. Various C3-functionalized cyclopentanyltetrahydrofurans (Cp-THF) were designed to interact with the flap Gly48 carbonyl or amide NH in the S2-subsite of the HIV-1 protease. We investigated the potential of those functionalized ligands in combination with hydroxyethylsulfonamide isosteres. Inhibitor 26 containing a 3-(R)-hydroxyl group on the Cp-THF core displayed the most potent enzyme inhibitory and antiviral activity. Our studies revealed a preference for the 3-(R)-configuration over the corresponding 3-(S)-derivative. Inhibitor 26 exhibited potent activity against a panel of multidrug-resistant HIV-1 variants. A high resolution X-ray structure of 26-bound HIV-1 protease revealed important molecular insight into the ligand-binding site interactions. | ||
| - | + | Design of HIV-1 Protease Inhibitors with C3-Substituted Hexahydrocyclopentafuranyl Urethanes as P2-Ligands: Synthesis, Biological Evaluation, and Protein-Ligand X-ray Crystal Structure.,Ghosh AK, Chapsal BD, Parham GL, Steffey M, Agniswamy J, Wang YF, Amano M, Weber IT, Mitsuya H J Med Chem. 2011 Jul 29. PMID:21800876<ref>PMID:21800876</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Virus protease|Virus protease]] | *[[Virus protease|Virus protease]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
| - | + | [[Category: Agniswamy, J]] | |
| - | [[Category: Agniswamy, J | + | [[Category: Wang, Y F]] |
| - | [[Category: Wang, Y F | + | [[Category: Weber, I T]] |
| - | [[Category: Weber, I T | + | |
[[Category: Aspartic acid protease]] | [[Category: Aspartic acid protease]] | ||
[[Category: C3-substituted hexahydrocyclopentafuranyl urethane as p2-ligand]] | [[Category: C3-substituted hexahydrocyclopentafuranyl urethane as p2-ligand]] | ||
[[Category: Hiv-1 protease inhibitor grl-0489a]] | [[Category: Hiv-1 protease inhibitor grl-0489a]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 12:36, 9 December 2014
Crystal structure of wild-type HIV-1 protease with C3-Substituted Hexahydrocyclopentafuranyl Urethane as P2-Ligand, GRL-0489A
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