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==Crystal Structure of the Human LIMK2 Kinase Domain In Complex With a Non-ATP Competitive Inhibitor==
==Crystal Structure of the Human LIMK2 Kinase Domain In Complex With a Non-ATP Competitive Inhibitor==
<StructureSection load='4tpt' size='340' side='right' caption='[[4tpt]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='4tpt' size='340' side='right'caption='[[4tpt]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4tpt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TPT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TPT FirstGlance]. <br>
<table><tr><td colspan='2'>[[4tpt]] 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=4TPT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TPT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=35H:N-{4-[(1S)-1,2-DIHYDROXYETHYL]BENZYL}-N-METHYL-4-(PHENYLSULFAMOYL)BENZAMIDE'>35H</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=35H:N-{4-[(1S)-1,2-DIHYDROXYETHYL]BENZYL}-N-METHYL-4-(PHENYLSULFAMOYL)BENZAMIDE'>35H</scene></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=4tpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tpt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tpt RCSB], [http://www.ebi.ac.uk/pdbsum/4tpt PDBsum]</span></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=4tpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tpt OCA], [https://pdbe.org/4tpt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tpt RCSB], [https://www.ebi.ac.uk/pdbsum/4tpt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tpt ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>
[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 ==
The first allosteric, type III inhibitor of LIM-kinase 2 (LIMK2) is reported. A series of molecules that feature both an N-phenylsulfonamide and tertiary amide were not only very potent at LIMK2 but also were extremely selective against a panel of other kinases. Enzymatic kinetic studies showed these molecules to be noncompetitive with ATP, suggesting allosteric inhibition. X-ray crystallography confirmed that these sulfonamides are a rare example of a type III kinase inhibitor that binds away from the highly conserved hinge region and instead resides in the hydrophobic pocket formed in the DFG-out conformation of the kinase, thus accounting for the high level of selectivity observed.
 
Discovery of a Type III Inhibitor of LIM Kinase 2 That Binds in a DFG-Out Conformation.,Goodwin NC, Cianchetta G, Burgoon HA, Healy J, Mabon R, Strobel ED, Allen J, Wang S, Hamman BD, Rawlins DB ACS Med Chem Lett. 2014 Aug 7;6(1):53-7. doi: 10.1021/ml500242y. eCollection 2015, Jan 8. PMID:25589930<ref>PMID:25589930</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4tpt" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Homo sapiens]]
[[Category: Burgoon, H A]]
[[Category: Large Structures]]
[[Category: Cianchetta, G]]
[[Category: Burgoon HA]]
[[Category: Goodwin, N C]]
[[Category: Cianchetta G]]
[[Category: Hamman, B L]]
[[Category: Goodwin NC]]
[[Category: Healy, J]]
[[Category: Hamman BL]]
[[Category: Mabon, S]]
[[Category: Healy J]]
[[Category: Rawlins, D B]]
[[Category: Mabon S]]
[[Category: Strobel, E D]]
[[Category: Rawlins DB]]
[[Category: Wang, S]]
[[Category: Strobel ED]]
[[Category: Dfg inhibitor]]
[[Category: Wang S]]
[[Category: Limk2 kinase]]
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