4pie

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'''Unreleased structure'''
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==Crystal structure of human adenovirus 2 protease a substrate based nitrile inhibitor==
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<StructureSection load='4pie' size='340' side='right' caption='[[4pie]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4pie]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PIE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PIE FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FO:N-{(2S)-2-(3-CHLOROPHENYL)-2-[(METHYLSULFONYL)AMINO]ACETYL}-L-PHENYLALANYL-N-[(2Z)-2-IMINOETHYL]GLYCINAMIDE'>3FO</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4piq|4piq]], [[4pis|4pis]]</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenain Adenain], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.39 3.4.22.39] </span></td></tr>
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<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=4pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pie OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pie RCSB], [http://www.ebi.ac.uk/pdbsum/4pie 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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The cysteine protease adenain is the essential protease of adenovirus and, as such, represents a promising target for the treatment of ocular and other adenoviral infections. Through a concise two-pronged hit discovery approach we identified tetrapeptide nitrile 1 and pyrimidine nitrile 2 as complementary starting points for adenain inhibition. These hits enabled the first high-resolution X-ray cocrystal structures of adenain with inhibitors bound and revealed the binding mode of 1 and 2. The screening hits were optimized by a structure-guided medicinal chemistry strategy into low nanomolar drug-like inhibitors of adenain.
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The entry 4pie is ON HOLD
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Discovery and structure-based optimization of adenain inhibitors.,Mac Sweeney A, Grosche P, Ellis D, Combrink K, Erbel P, Hughes N, Sirockin F, Melkko S, Bernardi A, Ramage P, Jarousse N, Altmann E ACS Med Chem Lett. 2014 Jun 20;5(8):937-41. doi: 10.1021/ml500224t. eCollection, 2014 Aug 14. PMID:25147618<ref>PMID:25147618</ref>
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Authors: Mac Sweeney, A., Grosche, P., Ellis, D., Combrink, C., Erbel, C., Hughes, N., Sirockin, F., Melkko, S., Bernardi, A., Ramage, P., Jarousse, N., Altmann, E.
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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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Description: Crystal structure of human adenovirus 2 protease a substrate based nitrile inhibitor
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Adenain]]
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[[Category: Altmann, E.]]
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[[Category: Bernardi, A.]]
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[[Category: Combrink, C.]]
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[[Category: Ellis, D.]]
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[[Category: Erbel, C.]]
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[[Category: Grosche, P.]]
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[[Category: Hughes, N.]]
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[[Category: Jarousse, N.]]
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[[Category: Melkko, S.]]
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[[Category: Ramage, P.]]
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[[Category: Sirockin, F.]]
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[[Category: Sweeney, A Mac.]]
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[[Category: Adenain]]
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[[Category: Adenovirus]]
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[[Category: Cofactor]]
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[[Category: Cysteine protease]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Pvic]]

Revision as of 09:51, 10 September 2014

Crystal structure of human adenovirus 2 protease a substrate based nitrile inhibitor

4pie, resolution 1.94Å

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