2h9v
From Proteopedia
(New page: 200px<br /><applet load="2h9v" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h9v, resolution 3.100Å" /> '''Structural basis fo...) |
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| - | [[Image:2h9v.gif|left|200px]]<br /><applet load="2h9v" size=" | + | [[Image:2h9v.gif|left|200px]]<br /><applet load="2h9v" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2h9v, resolution 3.100Å" /> | caption="2h9v, resolution 3.100Å" /> | ||
'''Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y27632'''<br /> | '''Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y27632'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Rho-kinase is a main player in the regulation of cytoskeletal events and a | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2H9V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with Y27 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2H9V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=Y27:'>Y27</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H9V OCA]. |
==Reference== | ==Reference== | ||
| - | 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 | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16891330 16891330] |
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
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[[Category: protein kinase-inhibitor complex]] | [[Category: protein kinase-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:39:42 2008'' |
Revision as of 15:39, 21 February 2008
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Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y27632
Overview
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.
About this Structure
2H9V is a Single protein structure of sequence from Bos taurus with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:39:42 2008
