2oc0: Difference between revisions

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-[[Image:2oc0.png|left|200px]]
+==Structure of NS3 complexed with a ketoamide inhibitor SCh491762==
+<StructureSection load='2oc0' size='340' side='right' caption='[[2oc0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2oc0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OC0 OCA]. <br>
+</td></tr><tr><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><br>
+<tr><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><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 Hepatitis C virus])</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
+<tr><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>
+<table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The 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<ref>PMID:17444623</ref>
-The line below this paragraph, containing "STRUCTURE_2oc0", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_2oc0|  PDB=2oc0  |  SCENE=  }}
-===Structure of NS3 complexed with a ketoamide inhibitor SCh491762===
+From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+</div>
+== References ==
-<!--
+<references/>
-The line below this paragraph, {{ABSTRACT_PUBMED_17444623}}, adds the Publication Abstract to the page
+__TOC__
-(as it appears on PubMed at http://www.pubmed.gov), where 17444623 is the PubMed ID number.
+</StructureSection>
--->
-{{ABSTRACT_PUBMED_17444623}}
-==About this Structure==
-[[2oc0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OC0 OCA].
-==Reference==
-<ref group="xtra">PMID:017444623</ref><ref group="xtra">PMID:008861917</ref><ref group="xtra">PMID:016087332</ref><ref group="xtra">PMID:016112859</ref><ref group="xtra">PMID:016112862</ref><ref group="xtra">PMID:016352601</ref><references group="xtra"/>
 [[Category: Hepatitis c virus]]
 [[Category: Arasappan, A.]]