1q8u

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (00:23, 21 November 2024) (edit) (undo)
 
(13 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1q8u.jpg|left|200px]]
 
-
{{Structure
+
==The Catalytic Subunit of cAMP-dependent Protein Kinase in Complex with Rho-kinase Inhibitor H-1152P==
-
|PDB= 1q8u |SIZE=350|CAPTION= <scene name='initialview01'>1q8u</scene>, resolution 1.90&Aring;
+
<StructureSection load='1q8u' size='340' side='right'caption='[[1q8u]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=H52:(S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE'>H52</scene> and <scene name='pdbligand=MG8:N-OCTANOYL-N-METHYLGLUCAMINE'>MG8</scene>
+
<table><tr><td colspan='2'>[[1q8u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q8U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q8U FirstGlance]. <br>
-
|ACTIVITY= [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]
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-
|GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H52:(S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE'>H52</scene>, <scene name='pdbligand=MG8:N-OCTANOYL-N-METHYLGLUCAMINE'>MG8</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=1q8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q8u OCA], [https://pdbe.org/1q8u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q8u RCSB], [https://www.ebi.ac.uk/pdbsum/1q8u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q8u ProSAT]</span></td></tr>
 +
</table>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q8/1q8u_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1q8u ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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.
-
'''The Catalytic Subunit of cAMP-dependent Protein Kinase in Complex with Rho-kinase Inhibitor H-1152P'''
+
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<ref>PMID:14656443</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 1q8u" style="background-color:#fffaf0;"></div>
-
==Overview==
+
==See Also==
-
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.
+
*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
1Q8U is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q8U OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==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:[http://www.ncbi.nlm.nih.gov/pubmed/14656443 14656443]
+
[[Category: Bos taurus]]
[[Category: Bos taurus]]
-
[[Category: Non-specific serine/threonine protein kinase]]
+
[[Category: Homo sapiens]]
-
[[Category: Protein complex]]
+
[[Category: Large Structures]]
-
[[Category: Bossemeyer, D.]]
+
[[Category: Bossemeyer D]]
-
[[Category: Breitenlechner, C.]]
+
[[Category: Breitenlechner C]]
-
[[Category: Engh, R A.]]
+
[[Category: Engh RA]]
-
[[Category: Gassel, M.]]
+
[[Category: Gassel M]]
-
[[Category: Hidaka, H.]]
+
[[Category: Hidaka H]]
-
[[Category: Huber, R.]]
+
[[Category: Huber R]]
-
[[Category: Kinzel, V.]]
+
[[Category: Kinzel V]]
-
[[Category: H52]]
+
-
[[Category: MG8]]
+
-
[[Category: atp-binding]]
+
-
[[Category: camp]]
+
-
[[Category: kinase-inhibitor-complex]]
+
-
[[Category: phosphorylation]]
+
-
[[Category: phosphotransferase/inhibitor]]
+
-
[[Category: pka]]
+
-
[[Category: rho-kinase]]
+
-
[[Category: serine/threonine-protein kinase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:34:28 2008''
+

Current revision

The Catalytic Subunit of cAMP-dependent Protein Kinase in Complex with Rho-kinase Inhibitor H-1152P

PDB ID 1q8u

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1q8u"
Personal tools