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4a1v

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[[Image:4a1v.png|left|200px]]
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==Co-Complex structure of NS3-4A protease with the optimized inhibitory peptide CP5-46A-4D5E==
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<StructureSection load='4a1v' size='340' side='right' caption='[[4a1v]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4a1v]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1b Hepatitis c virus subtype 1b]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A1V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A1V FirstGlance]. <br>
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</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=K:POTASSIUM+ION'>K</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1w3c|1w3c]], [[1dxp|1dxp]], [[1dy8|1dy8]], [[1dy9|1dy9]], [[4a1t|4a1t]], [[4a1x|4a1x]]</td></tr>
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<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=4a1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a1v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a1v RCSB], [http://www.ebi.ac.uk/pdbsum/4a1v PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Hepatitis C virus (HCV) NS3-4A protease is essential for viral replication. All current small molecular weight drugs against NS3-4A are substrate peptidomimetics that have a similar binding and resistance profile. We developed inhibitory peptides (IPs) capping the active site and binding via a novel "tyrosine" finger at an alternative NS3-4A site that is of particular interest for further HCV drug development. The peptides are not cleaved due to a combination of geometrical constraints and impairment of the oxyanion hole function. Selection and optimization through combinatorial phagemid display, protein crystallography, and further modifications resulted in a 32-amino acid peptide with a K(i) of 0.53 nm. Inhibition of viral replication in cell culture was demonstrated by fusion to a cell-penetrating peptide. Negligible susceptibility to known (A156V and R155K) resistance mutations of the NS3-4A protease was observed. This work shows for the first time that antiviral peptides can target an intracellular site and reveals a novel druggable site on the HCV protease.
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{{STRUCTURE_4a1v| PDB=4a1v | SCENE= }}
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High Affinity Peptide Inhibitors of the Hepatitis C Virus NS3-4A Protease Refractory to Common Resistant Mutants.,Kugler J, Schmelz S, Gentzsch J, Haid S, Pollmann E, van den Heuvel J, Franke R, Pietschmann T, Heinz DW, Collins J J Biol Chem. 2012 Nov 9;287(46):39224-32. doi: 10.1074/jbc.M112.393843. Epub 2012, Sep 10. PMID:22965230<ref>PMID:22965230</ref>
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===Co-Complex structure of NS3-4A protease with the optimized inhibitory peptide CP5-46A-4D5E===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_22965230}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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[[4a1v]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1b Hepatitis c virus subtype 1b]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A1V OCA].
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</StructureSection>
[[Category: Hepatitis c virus subtype 1b]]
[[Category: Hepatitis c virus subtype 1b]]
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[[Category: Collins, J.]]
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[[Category: Collins, J]]
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[[Category: Heinz, D W.]]
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[[Category: Heinz, D W]]
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[[Category: Kuegler, J.]]
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[[Category: Kuegler, J]]
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[[Category: Schmelz, S.]]
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[[Category: Schmelz, S]]
[[Category: Hydrolase-peptide complex]]
[[Category: Hydrolase-peptide complex]]

Revision as of 16:28, 9 December 2014

Co-Complex structure of NS3-4A protease with the optimized inhibitory peptide CP5-46A-4D5E

4a1v, resolution 2.20Å

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