2oc0: Difference between revisions
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<StructureSection load='2oc0' size='340' side='right' caption='[[2oc0]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='2oc0' size='340' side='right' caption='[[2oc0]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2oc0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2oc0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OC0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OC0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=HU1:TERT-BUTYL+{(1S)-2-[(1R,2S,5S)-2-({[(1S)-3-AMINO-1-(CYCLOBUTYLMETHYL)-2,3-DIOXOPROPYL]AMINO}CARBONYL)-6,6-DIMETHYL-3-AZABICYCLO[3.1.0]HEX-3-YL]-1-CYCLOHEXYL-2-OXOETHYL}CARBAMATE'>HU1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=HU1:TERT-BUTYL+{(1S)-2-[(1R,2S,5S)-2-({[(1S)-3-AMINO-1-(CYCLOBUTYLMETHYL)-2,3-DIOXOPROPYL]AMINO}CARBONYL)-6,6-DIMETHYL-3-AZABICYCLO[3.1.0]HEX-3-YL]-1-CYCLOHEXYL-2-OXOETHYL}CARBAMATE'>HU1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a1r|1a1r]], [[2a4g|2a4g]], [[2a4q|2a4q]], [[2a4r|2a4r]], [[2fm2|2fm2]], [[2f9v|2f9v]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a1r|1a1r]], [[2a4g|2a4g]], [[2a4q|2a4q]], [[2a4r|2a4r]], [[2fm2|2fm2]], [[2f9v|2f9v]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 9HEPC])</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=2oc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oc0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2oc0 RCSB], [http://www.ebi.ac.uk/pdbsum/2oc0 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=2oc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oc0 OCA], [http://pdbe.org/2oc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2oc0 RCSB], [http://www.ebi.ac.uk/pdbsum/2oc0 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
<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 2oc0" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Arasappan, A]] | [[Category: Arasappan, A]] | ||
[[Category: Bennett, F]] | [[Category: Bennett, F]] | ||
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[[Category: Zhang, R]] | [[Category: Zhang, R]] | ||
[[Category: Hcv]] | [[Category: Hcv]] | ||
[[Category: Hepatitis c virus]] | |||
[[Category: Ketoamide inhibitor]] | [[Category: Ketoamide inhibitor]] | ||
[[Category: Ns3 protease domain]] | [[Category: Ns3 protease domain]] | ||
[[Category: Viral protein]] | [[Category: Viral protein]] | ||
Revision as of 10:02, 10 September 2015
Structure of NS3 complexed with a ketoamide inhibitor SCh491762Structure of NS3 complexed with a ketoamide inhibitor SCh491762
Structural highlights
Publication Abstract from PubMedThe structures of both the native holo-HCV NS3/4A protease domain and the protease domain with a serine 139 to alanine (S139A) mutation were solved to high resolution. Subsequently, structures were determined for a series of ketoamide inhibitors in complex with the protease. The changes in the inhibitor potency were correlated with changes in the buried surface area upon binding the inhibitor to the active site. The largest contribution to the binding energy arises from the hydrophobic interactions of the P1 and P2 groups as they bind to the S1 and S2 pockets [the numbering of the subsites is as defined in Berger, A.; Schechter, I. Philos. Trans. R. Soc. London, Ser. B 1970, 257, 249-264]. This correlation of the changes in potency with increased buried surface area contributed directly to the design of a potent tripeptide inhibitor of the HCV NS3/4A protease that is currently in clinical trials. Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl] - 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (Sch 503034) II. Key steps in structure-based optimization.,Prongay AJ, Guo Z, Yao N, Pichardo J, Fischmann T, Strickland C, Myers J Jr, Weber PC, Beyer BM, Ingram R, Hong Z, Prosise WW, Ramanathan L, Taremi SS, Yarosh-Tomaine T, Zhang R, Senior M, Yang RS, Malcolm B, Arasappan A, Bennett F, Bogen SL, Chen K, Jao E, Liu YT, Lovey RG, Saksena AK, Venkatraman S, Girijavallabhan V, Njoroge FG, Madison V J Med Chem. 2007 May 17;50(10):2310-8. Epub 2007 Apr 20. PMID:17444623[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Arasappan, A
- Bennett, F
- Beyer, B M
- Bogen, S F
- Chen, K
- Fischmann, T
- Girijavallabhan, V
- Guo, Z
- Hong, Z
- Ingram, R
- Jao, E
- Liu, Y
- Love, R G
- Madison, V
- Malcolm, B
- Myers, J
- Njoroge, F G
- Pichardo, J
- Prongay, A J
- Prosise, W W
- Ramanathan, L
- Saksena, A K
- Senior, M
- Strickland, C
- Taremi, S S
- Venkatraman, S
- Weber, P C
- Yang, R
- Yao, N
- Yarosh-Tomaine, T
- Zhang, R
- Hcv
- Hepatitis c virus
- Ketoamide inhibitor
- Ns3 protease domain
- Viral protein