3ndm

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<StructureSection load='3ndm' size='340' side='right'caption='[[3ndm]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
<StructureSection load='3ndm' size='340' side='right'caption='[[3ndm]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3ndm]] is a 4 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=3NDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NDM FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3ndm]] is a 4 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=3NDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NDM FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3ND:(3S,4R)-N-(7-CHLORO-1-OXO-1,4-DIHYDROISOQUINOLIN-6-YL)-4-(4-CHLOROPHENYL)PYRROLIDINE-3-CARBOXAMIDE'>3ND</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ncz|3ncz]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3ND:(3S,4R)-N-(7-CHLORO-1-OXO-1,4-DIHYDROISOQUINOLIN-6-YL)-4-(4-CHLOROPHENYL)PYRROLIDINE-3-CARBOXAMIDE'>3ND</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ndm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ndm OCA], [https://pdbe.org/3ndm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ndm RCSB], [https://www.ebi.ac.uk/pdbsum/3ndm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ndm ProSAT]</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=3ndm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ndm OCA], [https://pdbe.org/3ndm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ndm RCSB], [https://www.ebi.ac.uk/pdbsum/3ndm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ndm ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://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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[https://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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The discovery and SAR of a series of beta-aryl substituted pyrrolidine 2H-isoquinolin-1-one inhibitors of Rho-kinase (ROCK) derived from 2 is herein described. SAR studies have shown that aryl groups in the beta-position are optimal for potency. Our efforts focused on improving the ROCK potency of this isoquinolone class of inhibitors which led to the identification of pyrrolidine 32 which demonstrated a 10-fold improvement in aortic ring (AR) potency over 2.
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Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 3, aryl substituted pyrrolidines.,Bosanac T, Hickey ER, Ginn J, Kashem M, Kerr S, Kugler S, Li X, Olague A, Schlyer S, Young ER Bioorg Med Chem Lett. 2010 Jun 15;20(12):3746-9. Epub 2010 Apr 21. PMID:20471253<ref>PMID:20471253</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 3ndm" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Rho-associated protein kinase|Rho-associated protein kinase]]
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Transferase]]
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[[Category: Li X]]
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[[Category: Li, X]]
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[[Category: Dimerization]]
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[[Category: Phosphorylation]]
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[[Category: Rho kinase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Crystal structure of Rho-Associated Protein Kinase (ROCK1) with a potent isoquinolone derivative

PDB ID 3ndm

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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