4a1t
From Proteopedia
(Difference between revisions)
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| - | [[ | + | ==Co-Complex of the of NS3-4A protease with the inhibitory peptide CP5- 46-A (in-House data)== |
| + | <StructureSection load='4a1t' size='340' side='right' caption='[[4a1t]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4a1t]] 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=4A1T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A1T FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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">[[1w3c|1w3c]], [[1dxp|1dxp]], [[1dy9|1dy9]], [[4a1x|4a1x]], [[4a1v|4a1v]]</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=4a1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a1t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a1t RCSB], [http://www.ebi.ac.uk/pdbsum/4a1t PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| - | + | ==See Also== | |
| - | + | *[[Nonstructural protein|Nonstructural protein]] | |
| - | == | + | == References == |
| - | [[ | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Hepatitis c virus subtype 1b]] | [[Category: Hepatitis c virus subtype 1b]] | ||
| - | [[Category: Collins, J | + | [[Category: Collins, J]] |
| - | [[Category: Heinz, D W | + | [[Category: Heinz, D W]] |
| - | [[Category: Kuegler, J | + | [[Category: Kuegler, J]] |
| - | [[Category: Schmelz, S | + | [[Category: Schmelz, S]] |
[[Category: Hydrolase-peptide complex]] | [[Category: Hydrolase-peptide complex]] | ||
[[Category: Unmodified inhibitory peptide]] | [[Category: Unmodified inhibitory peptide]] | ||
Revision as of 16:00, 9 December 2014
Co-Complex of the of NS3-4A protease with the inhibitory peptide CP5- 46-A (in-House data)
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