4tpt
From Proteopedia
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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]] 2.60Å' scene=''> | + | <StructureSection load='4tpt' size='340' side='right'caption='[[4tpt]], [[Resolution|resolution]] 2.60Å' 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 [ | + | <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=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | <tr id=' | + | <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'>[ | + | <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 == | ||
| - | [ | + | [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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, 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: | + | [[Category: Homo sapiens]] |
| - | [[Category: Burgoon | + | [[Category: Large Structures]] |
| - | [[Category: Cianchetta | + | [[Category: Burgoon HA]] |
| - | [[Category: Goodwin | + | [[Category: Cianchetta G]] |
| - | [[Category: Hamman | + | [[Category: Goodwin NC]] |
| - | [[Category: Healy | + | [[Category: Hamman BL]] |
| - | [[Category: Mabon | + | [[Category: Healy J]] |
| - | [[Category: Rawlins | + | [[Category: Mabon S]] |
| - | [[Category: Strobel | + | [[Category: Rawlins DB]] |
| - | [[Category: Wang | + | [[Category: Strobel ED]] |
| - | + | [[Category: Wang S]] | |
| - | + | ||
Current revision
Crystal Structure of the Human LIMK2 Kinase Domain In Complex With a Non-ATP Competitive Inhibitor
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Categories: Homo sapiens | Large Structures | Burgoon HA | Cianchetta G | Goodwin NC | Hamman BL | Healy J | Mabon S | Rawlins DB | Strobel ED | Wang S
