5hvu

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<StructureSection load='5hvu' size='340' side='right' caption='[[5hvu]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
<StructureSection load='5hvu' size='340' side='right' caption='[[5hvu]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5hvu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HVU FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5hvu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HVU FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=65R:2-{3-[3-(PIPERIDIN-4-YL)PROPOXY]PHENYL}-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>65R</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=65R:2-{3-[3-(PIPERIDIN-4-YL)PROPOXY]PHENYL}-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>65R</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 HUMAN])</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='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='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=5hvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hvu OCA], [http://pdbe.org/5hvu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hvu RCSB], [http://www.ebi.ac.uk/pdbsum/5hvu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hvu ProSAT]</span></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=5hvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hvu OCA], [http://pdbe.org/5hvu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hvu RCSB], [http://www.ebi.ac.uk/pdbsum/5hvu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hvu ProSAT]</span></td></tr>
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== Function ==
== Function ==
[[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>
[[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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Solubilizing groups have been frequently appended to kinase inhibitor drug molecules when solubility is insufficient for pharmaceutical development. Such groups are usually located at substitution sites that have minimal impact on target activity. In this report we describe the incorporation of solubilizing groups in a class of Rho kinase (ROCK) inhibitors that not only confer improved solubility, but also enhance target potency and selectivity against a closely related kinase, PKA.
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ROCK inhibitors 2. Improving potency, selectivity and solubility through the application of rationally designed solubilizing groups.,Gao H, Marhefka C, Jacobs MD, Cao J, Bandarage UK, Green J Bioorg Med Chem Lett. 2018 Jun 21. pii: S0960-894X(18)30532-8. doi:, 10.1016/j.bmcl.2018.06.043. PMID:29945794<ref>PMID:29945794</ref>
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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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<div class="pdbe-citations 5hvu" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Rho-associated protein kinase|Rho-associated protein kinase]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Jacobs, M J]]
[[Category: Jacobs, M J]]

Revision as of 08:45, 18 July 2018

Rho-associated protein kinase 1 (ROCK 1) in complex with a pyridine thiazole piperidine inhibitor

5hvu, resolution 2.80Å

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