View source for 4wx7


==Crystal structure of adenovirus 8 protease with a nitrile inhibitor==
<StructureSection load='4wx7' size='340' side='right'caption='[[4wx7]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wx7]] is a 4 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=4WX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WX7 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3VJ:3-[2-(3,5-DICHLOROPHENYL)-2-METHYLPROPANOYL]-N-(2-{[(2Z)-2-IMINOETHYL]AMINO}-2-OXOETHYL)-4-METHOXYBENZAMIDE'>3VJ</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=4wx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wx7 OCA], [https://pdbe.org/4wx7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wx7 RCSB], [https://www.ebi.ac.uk/pdbsum/4wx7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wx7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B9A5C1_ADE08 B9A5C1_ADE08] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Adenoviral infections are associated with a wide range of acute diseases, among which ocular viral conjunctivitis (EKC) and disseminated disease in immunocompromised patients. To date, no approved specific anti-adenoviral drug is available, but there is a growing need for an effective treatment of such infections. The adenoviral protease, adenain, plays a crucial role for the viral lifecycle and thus represents an attractive therapeutic target. Structure-guided design with the objective to depeptidize tetrapeptide nitrile 1 led to the novel chemotype 2. Optimization of scaffold 2 resulted in picomolar adenain inhibitors 3a and 3b. In addition, a complementary series of irreversible vinyl sulfone containing inhibitors were rationally designed, prepared and evaluated against adenoviral protease. High resolution X-ray co-crystal structures of representatives of each series proves the successful design of these inhibitors and provides an excellent basis for future medicinal chemistry optimization of these compounds.

Structure-based design and optimization of potent inhibitors of the adenoviral protease.,Grosche P, Sirockin F, Mac Sweeney A, Ramage P, Erbel P, Melkko S, Bernardi A, Hughes N, Ellis D, Combrink KD, Jarousse N, Altmann E Bioorg Med Chem Lett. 2015 Feb 1;25(3):438-43. doi: 10.1016/j.bmcl.2014.12.057., Epub 2014 Dec 24. PMID:25571794<ref>PMID:25571794</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wx7" 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]]