View source for 4y8d


==Crystal structure of Cyclin-G associated kinase (GAK) complexed with selective 12i inhibitor==
<StructureSection load='4y8d' size='340' side='right'caption='[[4y8d]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4y8d]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y8D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y8D 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=49J:2-METHOXY-4-[3-(MORPHOLIN-4-YL)[1,2]THIAZOLO[4,3-B]PYRIDIN-6-YL]ANILINE'>49J</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4y8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y8d OCA], [https://pdbe.org/4y8d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y8d RCSB], [https://www.ebi.ac.uk/pdbsum/4y8d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y8d ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GAK_HUMAN GAK_HUMAN] Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1.<ref>PMID:10625686</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cyclin-G associated kinase (GAK) emerged as a promising drug target for the treatment of viral infections. However, no potent and selective GAK inhibitors have been reported in the literature to date. This paper describes the discovery of isothiazolo[5,4-b]pyridines as selective GAK inhibitors, with the most potent congeners displaying low nanomolar binding affinity for GAK. Co-crystallization experiments revealed that these compounds behaved as classic type I ATP-competitive kinase inhibitors. In addition, we have demonstrated that these compounds exhibit a potent activity against hepatitis C virus (HCV) by inhibiting two temporally distinct steps in the HCV lifecycle (i.e. viral entry and assembly). Hence, these GAK inhibitors represent chemical probes to study GAK function in different disease areas where GAK has been implicated (including viral infection, cancer and Parkinson's disease).

Selective inhibitors of Cyclin-G associated kinase (GAK) as anti-HCV agents.,Kovackova S, Chang L, Bekerman E, Neveu G, Barouch-Bentov R, Chaikuad A, Heroven C, Sala M, De Jonghe SC, Knapp S, Einav S, Herdewijn P J Med Chem. 2015 Mar 30. PMID:25822739<ref>PMID:25822739</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4y8d" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Chaikuad A]]
[[Category: De Jonghe S]]
[[Category: Edwards AM]]
[[Category: Heroven C]]
[[Category: Knapp S]]
[[Category: Nowak R]]
[[Category: Von Delft F]]