3s95

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the human LIMK1 kinase domain in complex with staurosporine

Structural highlights

3s95 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.65Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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

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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

References

↑ Edwards DC, Gill GN. Structural features of LIM kinase that control effects on the actin cytoskeleton. J Biol Chem. 1999 Apr 16;274(16):11352-61. PMID:10196227
↑ Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 1999 Aug 6;285(5429):895-8. PMID:10436159
↑ Niwa R, Nagata-Ohashi K, Takeichi M, Mizuno K, Uemura T. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 2002 Jan 25;108(2):233-46. PMID:11832213
↑ Kaji N, Ohashi K, Shuin M, Niwa R, Uemura T, Mizuno K. Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells. J Biol Chem. 2003 Aug 29;278(35):33450-5. Epub 2003 Jun 14. PMID:12807904 doi:10.1074/jbc.M305802200
↑ Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, Sampath R, Bamburg JR, Bernard O. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005 Feb 9;24(3):473-86. Epub 2005 Jan 20. PMID:15660133 doi:7600543
↑ Nishita M, Tomizawa C, Yamamoto M, Horita Y, Ohashi K, Mizuno K. Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. J Cell Biol. 2005 Oct 24;171(2):349-59. Epub 2005 Oct 17. PMID:16230460 doi:10.1083/jcb.200504029
↑ Acevedo K, Li R, Soo P, Suryadinata R, Sarcevic B, Valova VA, Graham ME, Robinson PJ, Bernard O. The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules. Exp Cell Res. 2007 Dec 10;313(20):4091-106. PMID:18028908 doi:10.1016/j.yexcr.2007.08.012

1 Structural highlights
2 Disease
3 Function
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3s95"

@@ Line 3: / Line 3: @@
 <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/Human Human]. 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>
+<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='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>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LIMK, LIMK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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'>[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.
+[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>
+[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: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Allerston CK]]
-[[Category: Allerston, C K]]
+[[Category: Arrowsmith CH]]
-[[Category: Arrowsmith, C H]]
+[[Category: Beltrami A]]
-[[Category: Beltrami, A]]
+[[Category: Bountra C]]
-[[Category: Bountra, C]]
+[[Category: Bullock A]]
-[[Category: Bullock, A]]
+[[Category: Chaikuad A]]
-[[Category: Chaikuad, A]]
+[[Category: Daga N]]
-[[Category: Daga, N]]
+[[Category: Edwards AM]]
-[[Category: Delft, F von]]
+[[Category: Elkins JM]]
-[[Category: Edwards, A M]]
+[[Category: Fedorov O]]
-[[Category: Elkins, J M]]
+[[Category: Gileadi O]]
-[[Category: Fedorov, O]]
+[[Category: Knapp S]]
-[[Category: Gileadi, O]]
+[[Category: Krojer T]]
-[[Category: Knapp, S]]
+[[Category: Mahajan P]]
-[[Category: Krojer, T]]
+[[Category: Muniz JRC]]
-[[Category: Mahajan, P]]
+[[Category: Savitsky P]]
-[[Category: Muniz, J R.C]]
+[[Category: Vollmar M]]
-[[Category: Structural genomic]]
+[[Category: Weigelt J]]
-[[Category: Savitsky, P]]
+[[Category: Yue WW]]
-[[Category: Vollmar, M]]
+[[Category: Von Delft F]]
-[[Category: Weigelt, J]]
-[[Category: Yue, W W]]
-[[Category: Lim domain kinase]]
-[[Category: Protein kinase]]
-[[Category: Sgc]]
-[[Category: Transferase-antibiotic complex]]

3s95

From Proteopedia

Current revision

Crystal structure of the human LIMK1 kinase domain in complex with staurosporine

Structural highlights

Disease

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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