3ggv: Difference between revisions
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==HIV Protease, pseudo-symmetric inhibitors== | ==HIV Protease, pseudo-symmetric inhibitors== | ||
<StructureSection load='3ggv' size='340' side='right' caption='[[3ggv]], [[Resolution|resolution]] 3.09Å' scene=''> | <StructureSection load='3ggv' size='340' side='right' caption='[[3ggv]], [[Resolution|resolution]] 3.09Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ggv]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3ggv]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GGV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GGV:METHYL+[(1S)-1-{[(1R,3S,4S)-3-HYDROXY-4-{[(2S)-2-(3-{[6-(1-HYDROXY-1-METHYLETHYL)PYRIDIN-2-YL]METHYL}-2-OXO-2,3-DIHYDRO-1H-IMIDAZOL-1-YL)-3,3-DIMETHYLBUTANOYL]AMINO}-5-PHENYL-1-(4-PYRIDIN-2-YLBENZYL)PENTYL]CARBAMOYL}-2,2-DIMETHYLPROPYL]CARBAMATE'>GGV</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GGV:METHYL+[(1S)-1-{[(1R,3S,4S)-3-HYDROXY-4-{[(2S)-2-(3-{[6-(1-HYDROXY-1-METHYLETHYL)PYRIDIN-2-YL]METHYL}-2-OXO-2,3-DIHYDRO-1H-IMIDAZOL-1-YL)-3,3-DIMETHYLBUTANOYL]AMINO}-5-PHENYL-1-(4-PYRIDIN-2-YLBENZYL)PENTYL]CARBAMOYL}-2,2-DIMETHYLPROPYL]CARBAMATE'>GGV</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gga|3gga]], [[3ggx|3ggx]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gga|3gga]], [[3ggx|3ggx]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=3ggv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ggv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ggv RCSB], [http://www.ebi.ac.uk/pdbsum/3ggv PDBsum]</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=3ggv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ggv OCA], [http://pdbe.org/3ggv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ggv RCSB], [http://www.ebi.ac.uk/pdbsum/3ggv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ggv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ggv ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3ggv" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Stoll, V S]] | [[Category: Stoll, V S]] | ||
[[Category: Hiv protease]] | [[Category: Hiv protease]] | ||
Revision as of 17:45, 11 August 2016
HIV Protease, pseudo-symmetric inhibitorsHIV Protease, pseudo-symmetric inhibitors
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedA series of symmetry-based HIV protease inhibitors was designed and synthesized. Modification of the core regiochemistry and stereochemistry significantly affected the potency, metabolic stability, and oral bioavailability of the inhibitors, as did the variation of a pendent arylmethyl P3 group. Optimization led to the selection of two compounds, 10c (A-790742) and 9d (A-792611), for advancement to preclinical studies. Both compounds displayed low nanomolar potency against wild type HIV in the presence of human serum, low rates of metabolism in human liver microsomes, and high oral bioavailability in animal models. The compounds were examined in a preclinical model for the hyperbilirubinemia observed with some HIV PIs, and both exhibited less bilirubin elevation than comparator compounds. X-ray crystallographic analyses of the new cores were used to examine differences in their binding modes. The antiviral activity of the compounds against protease inhibitor resistant strains of HIV was also determined. 2-Pyridyl P1'-substituted symmetry-based human immunodeficiency virus protease inhibitors (A-792611 and A-790742) with potential for convenient dosing and reduced side effects.,Degoey DA, Grampovnik DJ, Flentge CA, Flosi WJ, Chen HJ, Yeung CM, Randolph JT, Klein LL, Dekhtyar T, Colletti L, Marsh KC, Stoll V, Mamo M, Morfitt DC, Nguyen B, Schmidt JM, Swanson SJ, Mo H, Kati WM, Molla A, Kempf DJ J Med Chem. 2009 Apr 23;52(8):2571-86. PMID:19323562[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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