1q8t: Difference between revisions
New page: left|200px<br /><applet load="1q8t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q8t, resolution 2.00Å" /> '''The Catalytic Subuni... |
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[[Image:1q8t.jpg|left|200px]]<br /><applet load="1q8t" size=" | [[Image:1q8t.jpg|left|200px]]<br /><applet load="1q8t" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1q8t, resolution 2.00Å" /> | caption="1q8t, resolution 2.00Å" /> | ||
'''The Catalytic Subunit of cAMP-dependent Protein Kinase (PKA) in Complex with Rho-kinase Inhibitor Y-27632'''<br /> | '''The Catalytic Subunit of cAMP-dependent Protein Kinase (PKA) in Complex with Rho-kinase Inhibitor Y-27632'''<br /> | ||
==Overview== | ==Overview== | ||
Protein kinases require strict inactivation to prevent spurious cellular | Protein kinases require strict inactivation to prevent spurious cellular signaling; overactivity can cause cancer or other diseases and necessitates selective inhibition for therapy. Rho-kinase is involved in such processes as tumor invasion, cell adhesion, smooth muscle contraction, and formation of focal adhesion fibers, as revealed using inhibitor Y-27632. Another Rho-kinase inhibitor, HA-1077 or Fasudil, is currently used in the treatment of cerebral vasospasm; the related nanomolar inhibitor H-1152P improves on its selectivity and potency. We have determined the crystal structures of HA-1077, H-1152P, and Y-27632 in complexes with protein kinase A (PKA) as a surrogate kinase to analyze Rho-kinase inhibitor binding properties. Features conserved between PKA and Rho-kinase are involved in the key binding interactions, while a combination of residues at the ATP binding pocket that are unique to Rho-kinase may explain the inhibitors' Rho-kinase selectivity. Further, a second H-1152P binding site potentially points toward PKA regulatory domain interaction modulators. | ||
==About this Structure== | ==About this Structure== | ||
1Q8T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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:// | 1Q8T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1Q8T OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Bossemeyer, D.]] | [[Category: Bossemeyer, D.]] | ||
[[Category: Breitenlechner, C.]] | [[Category: Breitenlechner, C.]] | ||
[[Category: Engh, R | [[Category: Engh, R A.]] | ||
[[Category: Gassel, M.]] | [[Category: Gassel, M.]] | ||
[[Category: Hidaka, H.]] | [[Category: Hidaka, H.]] | ||
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[[Category: serine/threonine-protein kinase]] | [[Category: serine/threonine-protein kinase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:37:12 2008'' | ||
Revision as of 12:37, 21 February 2008
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The Catalytic Subunit of cAMP-dependent Protein Kinase (PKA) in Complex with Rho-kinase Inhibitor Y-27632
Overview
Protein kinases require strict inactivation to prevent spurious cellular signaling; overactivity can cause cancer or other diseases and necessitates selective inhibition for therapy. Rho-kinase is involved in such processes as tumor invasion, cell adhesion, smooth muscle contraction, and formation of focal adhesion fibers, as revealed using inhibitor Y-27632. Another Rho-kinase inhibitor, HA-1077 or Fasudil, is currently used in the treatment of cerebral vasospasm; the related nanomolar inhibitor H-1152P improves on its selectivity and potency. We have determined the crystal structures of HA-1077, H-1152P, and Y-27632 in complexes with protein kinase A (PKA) as a surrogate kinase to analyze Rho-kinase inhibitor binding properties. Features conserved between PKA and Rho-kinase are involved in the key binding interactions, while a combination of residues at the ATP binding pocket that are unique to Rho-kinase may explain the inhibitors' Rho-kinase selectivity. Further, a second H-1152P binding site potentially points toward PKA regulatory domain interaction modulators.
About this Structure
1Q8T is a Protein complex structure of sequences from Bos taurus with Y27 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
Protein kinase A in complex with Rho-kinase inhibitors Y-27632, Fasudil, and H-1152P: structural basis of selectivity., Breitenlechner C, Gassel M, Hidaka H, Kinzel V, Huber R, Engh RA, Bossemeyer D, Structure. 2003 Dec;11(12):1595-607. PMID:14656443
Page seeded by OCA on Thu Feb 21 14:37:12 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Bos taurus
- Non-specific serine/threonine protein kinase
- Protein complex
- Bossemeyer, D.
- Breitenlechner, C.
- Engh, R A.
- Gassel, M.
- Hidaka, H.
- Huber, R.
- Kinzel, V.
- Y27
- Atp-binding
- Camp
- Kinase-inhibitor-complex
- Phosphorylation
- Phosphotransferase/inhibitor
- Pka
- Rho-kinase
- Serine/threonine-protein kinase
