2oc7

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[[Image:2oc7.jpg|left|200px]]
[[Image:2oc7.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2oc7 |SIZE=350|CAPTION= <scene name='initialview01'>2oc7</scene>, resolution 2.7&Aring;
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The line below this paragraph, containing "STRUCTURE_2oc7", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=HU4:TERT-BUTYL+{(1S)-2-[(1R,2S,5R)-2-({[(1S)-3-AMINO-1-(CYCLOBUTYLMETHYL)-2,3-DIOXOPROPYL]AMINO}CARBONYL)-7,7-DIMETHYL-6-OXA-3-AZABICYCLO[3.2.0]HEPT-3-YL]-1-CYCLOHEXYL-2-OXOETHYL}CARBAMATE'>HU4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE= NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 Hepatitis C virus])
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-->
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|DOMAIN=
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{{STRUCTURE_2oc7| PDB=2oc7 | SCENE= }}
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|RELATEDENTRY=[[2obo|2OBO]], [[2oc1|2OC1]], [[2oc0|2OC0]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oc7 OCA], [http://www.ebi.ac.uk/pdbsum/2oc7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oc7 RCSB]</span>
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}}
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'''Structure of Hepatitis C Viral NS3 protease domain complexed with NS4A peptide and ketoamide SCH571696'''
'''Structure of Hepatitis C Viral NS3 protease domain complexed with NS4A peptide and ketoamide SCH571696'''
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[[Category: Yarosh-Tomaine, T.]]
[[Category: Yarosh-Tomaine, T.]]
[[Category: Zhang, R.]]
[[Category: Zhang, R.]]
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[[Category: hcv]]
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[[Category: Hcv]]
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[[Category: hepatitis c virus]]
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[[Category: Hepatitis c virus]]
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[[Category: ketoamide inhibitor]]
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[[Category: Ketoamide inhibitor]]
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[[Category: ns3 protease domain]]
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[[Category: Ns3 protease domain]]
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[[Category: viral protein]]
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[[Category: Viral protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:35:23 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:15:43 2008''
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Revision as of 07:35, 4 May 2008

Image:2oc7.jpg

Template:STRUCTURE 2oc7

Structure of Hepatitis C Viral NS3 protease domain complexed with NS4A peptide and ketoamide SCH571696


Overview

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.

About this Structure

2OC7 is a Protein complex structure of sequences from Hepatitis c virus. Full crystallographic information is available from OCA.

Reference

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 Page seeded by OCA on Sun May 4 10:35:23 2008

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