3tv7

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[[Image:3tv7.png|left|200px]]
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==Human Rho-associated protein kinase 1 (ROCK 1) in COMPLEX WITH RKI1342==
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<StructureSection load='3tv7' size='340' side='right' caption='[[3tv7]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3tv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TV7 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07Q:1-[(1R)-1-(3-METHOXYPHENYL)ETHYL]-3-(4-PYRIDIN-4-YL-1,3-THIAZOL-2-YL)UREA'>07Q</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ROCK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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>
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<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=3tv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tv7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tv7 RCSB], [http://www.ebi.ac.uk/pdbsum/3tv7 PDBsum]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/ROCK1_HUMAN ROCK1_HUMAN]] Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation.<ref>PMID:8617235</ref> <ref>PMID:9722579</ref> <ref>PMID:10436159</ref> <ref>PMID:10652353</ref> <ref>PMID:11018042</ref> <ref>PMID:11283607</ref> <ref>PMID:17158456</ref> <ref>PMID:18694941</ref> <ref>PMID:18573880</ref> <ref>PMID:19036714</ref> <ref>PMID:19181962</ref> <ref>PMID:19131646</ref> <ref>PMID:19997641</ref> <ref>PMID:21072057</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Potent ROCK inhibitors of a new class of 1-benzyl-3-(4-pyridylthiazol-2-yl)ureas have been identified. Remarkable differences in activity were observed for ureas bearing a benzylic stereogenic center. Derivatives with hydroxy, methoxy and amino groups at the meta position of the phenyl ring give rise to the most potent inhibitors (low nM). Substitutions at the para position result in substantial loss of potency. Changes at the benzylic position are tolerated resulting in significant potency in the case of methyl and methylenehydroxy groups. X-Ray crystallography was used to establish the binding mode of this class of inhibitors and provides an explanation for the observed differences of the enantiomer series. Potent inhibition of ROCK in human lung cancer cells was shown by suppression of the levels of phosphorylation of the ROCK substrate MYPT-1.
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{{STRUCTURE_3tv7| PDB=3tv7 | SCENE= }}
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Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2).,Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schonbrunn E, Sebti SM, Lawrence NJ Medchemcomm. 2012 Jun 1;3(6):699-709. Epub 2012 Jan 27. PMID:23275831<ref>PMID:23275831</ref>
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===Human Rho-associated protein kinase 1 (ROCK 1) in COMPLEX WITH RKI1342===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_23275831}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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[[3tv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TV7 OCA].
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Martin, M P.]]
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[[Category: Martin, M P]]
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[[Category: Schonbrunn, E.]]
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[[Category: Schonbrunn, E]]
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[[Category: Zhu, J Y.]]
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[[Category: Zhu, J Y]]
[[Category: Dimer]]
[[Category: Dimer]]
[[Category: Dimerization]]
[[Category: Dimerization]]

Revision as of 02:14, 25 December 2014

Human Rho-associated protein kinase 1 (ROCK 1) in COMPLEX WITH RKI1342

3tv7, resolution 2.75Å

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