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2h9v

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Revision as of 06:11, 27 June 2018

Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y27632

Structural highlights

2h9v is a 1 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2f2u
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ROCK2_BOVIN] 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 ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Rho-kinase is a main player in the regulation of cytoskeletal events and a promising drug target in the treatment of both vascular and neurological disorders. Here we report the crystal structure of the Rho-kinase catalytic domain in complex with the specific inhibitor Y-27632. Comparison with the structure of PKA bound to this inhibitor revealed a potential induced-fit binding mode that can be accommodated by the phosphate binding loop. This binding mode resembles to that observed in the Rho-kinase-fasudil complex. A structural database search indicated that a pocket underneath the phosphate-binding loop is present that favors binding to a small aromatic ring. Introduction of such a ring group might spawn a new modification scheme of pre-existing protein kinase inhibitors for improved binding capability.

Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y-27632.,Yamaguchi H, Miwa Y, Kasa M, Kitano K, Amano M, Kaibuchi K, Hakoshima T J Biochem. 2006 Sep;140(3):305-11. Epub 2006 Aug 4. PMID:16891330^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, Nakano T, Okawa K, Iwamatsu A, Kaibuchi K. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J. 1996 May 1;15(9):2208-16. PMID:8641286
↑ Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem. 1996 Aug 23;271(34):20246-9. PMID:8702756
↑ Goto H, Kosako H, Tanabe K, Yanagida M, Sakurai M, Amano M, Kaibuchi K, Inagaki M. Phosphorylation of vimentin by Rho-associated kinase at a unique amino-terminal site that is specifically phosphorylated during cytokinesis. J Biol Chem. 1998 May 8;273(19):11728-36. PMID:9565595
↑ Matsui T, Maeda M, Doi Y, Yonemura S, Amano M, Kaibuchi K, Tsukita S, Tsukita S. Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J Cell Biol. 1998 Feb 9;140(3):647-57. PMID:9456324
↑ Fukata Y, Oshiro N, Kinoshita N, Kawano Y, Matsuoka Y, Bennett V, Matsuura Y, Kaibuchi K. Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility. J Cell Biol. 1999 Apr 19;145(2):347-61. PMID:10209029
↑ Kaneko T, Amano M, Maeda A, Goto H, Takahashi K, Ito M, Kaibuchi K. Identification of calponin as a novel substrate of Rho-kinase. Biochem Biophys Res Commun. 2000 Jun 24;273(1):110-6. PMID:10873572 doi:http://dx.doi.org/10.1006/bbrc.2000.2901
↑ Arimura N, Inagaki N, Chihara K, Menager C, Nakamura N, Amano M, Iwamatsu A, Goshima Y, Kaibuchi K. Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse. J Biol Chem. 2000 Aug 4;275(31):23973-80. PMID:10818093 doi:http://dx.doi.org/10.1074/jbc.M001032200
↑ Yamaguchi H, Miwa Y, Kasa M, Kitano K, Amano M, Kaibuchi K, Hakoshima T. Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y-27632. J Biochem. 2006 Sep;140(3):305-11. Epub 2006 Aug 4. PMID:16891330 doi:http://dx.doi.org/10.1093/jb/mvj172

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2h9v"

@@ Line 1: / Line 1: @@
 ==Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y27632==
 <StructureSection load='2h9v' size='340' side='right' caption='[[2h9v]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f2u|2f2u]]</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=2h9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h9v OCA], [http://pdbe.org/2h9v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2h9v RCSB], [http://www.ebi.ac.uk/pdbsum/2h9v PDBsum]</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=2h9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h9v OCA], [http://pdbe.org/2h9v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2h9v RCSB], [http://www.ebi.ac.uk/pdbsum/2h9v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2h9v ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h9/2h9v_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h9/2h9v_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 29: / Line 30: @@
 </div>
 <div class="pdbe-citations 2h9v" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Rho-associated protein kinase|Rho-associated protein kinase]]
 == References ==
 <references/>

2h9v

From Proteopedia

Revision as of 06:11, 27 June 2018

Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y27632

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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