View source for 4pis


==Crystal structure of human adenovirus 8 protease in complex with a nitrile inhibitor==
<StructureSection load='4pis' size='340' side='right'caption='[[4pis]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pis]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_adenovirus_D8 Human adenovirus D8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PIS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PIS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3FU:N~2~-[(2R)-2-(3,5-DICHLOROPHENYL)-2-(DIMETHYLAMINO)ACETYL]-N-({2-[(Z)-IMINOMETHYL]PYRIMIDIN-4-YL}METHYL)-L-ISOLEUCINAMIDE'>3FU</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4pis FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pis OCA], [https://pdbe.org/4pis PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pis RCSB], [https://www.ebi.ac.uk/pdbsum/4pis PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pis ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B9A5C1_ADE08 B9A5C1_ADE08] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4pis" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human adenovirus D8]]
[[Category: Large Structures]]
[[Category: Altmann E]]
[[Category: Bernardi A]]
[[Category: Combrink K]]
[[Category: Ellis D]]
[[Category: Erbel P]]
[[Category: Grosche P]]
[[Category: Hughes N]]
[[Category: Jarousse N]]
[[Category: Mac Sweeney A]]
[[Category: Melkko S]]
[[Category: Ramage P]]
[[Category: Sirockin F]]