View source for 7qhg


==LIM domain kinase 2 (LIMK2) in complex with TH-470==
<StructureSection load='7qhg' size='340' side='right'caption='[[7qhg]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qhg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QHG 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]] 1.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=T3B:2-(2-methylpropanoylamino)-~{N}-[2-[(phenylmethyl)-[4-(phenylsulfamoyl)phenyl]carbonyl-amino]ethyl]-1,3-thiazole-5-carboxamide'>T3B</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=7qhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qhg OCA], [https://pdbe.org/7qhg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qhg RCSB], [https://www.ebi.ac.uk/pdbsum/7qhg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qhg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LIMK2_HUMAN LIMK2_HUMAN] Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro.<ref>PMID:10436159</ref> <ref>PMID:11018042</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
LIMKs are important regulators of actin and microtubule dynamics, and they play essential roles in many cellular processes. Deregulation of LIMKs has been linked to the development of diverse diseases, including cancers and cognitive disabilities, but well-characterized inhibitors known as chemical probes are still lacking. Here, we report the characterization of three highly selective LIMK1/2 inhibitors covering all canonical binding modes (type I/II/III) and the structure-based design of the type II/III inhibitors. Characterization of these chemical probes revealed a low nanomolar affinity for LIMK1/2, and all inhibitors 1 (LIMKi3; type I), 48 (TH470; type II), and 15 (TH257; type III) showed excellent selectivity in a comprehensive scanMAX kinase selectivity panel. Phosphoproteomics revealed remarkable differences between type I and type II inhibitors compared with the allosteric inhibitor 15. In phenotypic assays such as neurite outgrowth models of fragile X-chromosome, 15 showed promising activity, suggesting the potential application of allosteric LIMK inhibitors treating this orphan disease.

Development and Characterization of Type I, Type II, and Type III LIM-Kinase Chemical Probes.,Hanke T, Mathea S, Woortman J, Salah E, Berger BT, Tumber A, Kashima R, Hata A, Kuster B, Muller S, Knapp S J Med Chem. 2022 Oct 13;65(19):13264-13287. doi: 10.1021/acs.jmedchem.2c01106. , Epub 2022 Sep 22. PMID:36136092<ref>PMID:36136092</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qhg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hanke T]]
[[Category: Knapp S]]
[[Category: Mathea S]]
[[Category: Salah E]]