View source for 3s95


==Crystal structure of the human LIMK1 kinase domain in complex with staurosporine==
<StructureSection load='3s95' size='340' side='right'caption='[[3s95]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3s95]] 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=3S95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S95 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]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=3s95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s95 OCA], [https://pdbe.org/3s95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s95 RCSB], [https://www.ebi.ac.uk/pdbsum/3s95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s95 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/LIMK1_HUMAN LIMK1_HUMAN] Williams syndrome. Note=LIMK1 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.
== Function ==
[https://www.uniprot.org/uniprot/LIMK1_HUMAN LIMK1_HUMAN] Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. Stimulates axonal outgrowth and may be involved in brain development. Isoform 3 has a dominant negative effect on actin cytoskeletal changes.<ref>PMID:10196227</ref> <ref>PMID:10436159</ref> <ref>PMID:11832213</ref> <ref>PMID:12807904</ref> <ref>PMID:15660133</ref> <ref>PMID:16230460</ref> <ref>PMID:18028908</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Allerston CK]]
[[Category: Arrowsmith CH]]
[[Category: Beltrami A]]
[[Category: Bountra C]]
[[Category: Bullock A]]
[[Category: Chaikuad A]]
[[Category: Daga N]]
[[Category: Edwards AM]]
[[Category: Elkins JM]]
[[Category: Fedorov O]]
[[Category: Gileadi O]]
[[Category: Knapp S]]
[[Category: Krojer T]]
[[Category: Mahajan P]]
[[Category: Muniz JRC]]
[[Category: Savitsky P]]
[[Category: Vollmar M]]
[[Category: Weigelt J]]
[[Category: Yue WW]]
[[Category: Von Delft F]]