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4y8d

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Revision as of 23:43, 5 June 2019

Crystal structure of Cyclin-G associated kinase (GAK) complexed with selective 12i inhibitor

Structural highlights

4y8d is a 4 chain structure with sequence from Human and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	GAK (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Greener T, Zhao X, Nojima H, Eisenberg E, Greene LE. Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells. J Biol Chem. 2000 Jan 14;275(2):1365-70. PMID:10625686
↑ 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. Selective inhibitors of Cyclin-G associated kinase (GAK) as anti-HCV agents. J Med Chem. 2015 Mar 30. PMID:25822739 doi:http://dx.doi.org/10.1021/jm501759m

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4y8d"

@@ Line 1: / Line 1: @@
 ==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=''>
+<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 [http://en.wikipedia.org/wiki/ ] and [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y8D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4y8d]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y8D FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GAK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=4y8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y8d OCA], [http://pdbe.org/4y8d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y8d RCSB], [http://www.ebi.ac.uk/pdbsum/4y8d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y8d ProSAT]</span></td></tr>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Lama glama]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Arrowsmith, C H]]

4y8d

From Proteopedia

Revision as of 23:43, 5 June 2019

Crystal structure of Cyclin-G associated kinase (GAK) complexed with selective 12i inhibitor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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