2gng: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2gng.png|left|200px]]
+==Protein kinase A fivefold mutant model of Rho-kinase==
+<StructureSection load='2gng' size='340' side='right' caption='[[2gng]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2gng]] is a 2 chain structure with sequence 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=2GNG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GNG FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1q8t|1q8t]], [[1q8u|1q8u]], [[1q8w|1q8w]], [[2gnf|2gnf]], [[2gnh|2gnh]], [[2gni|2gni]], [[2gnj|2gnj]], [[2gnl|2gnl]]</td></tr>
+<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span></td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gng OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gng RCSB], [http://www.ebi.ac.uk/pdbsum/2gng PDBsum]</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/gn/2gng_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Controlling aberrant kinase-mediated cellular signaling is a major strategy in cancer therapy; successful protein kinase inhibitors such as Tarceva and Gleevec verify this approach. Specificity of inhibitors for the targeted kinase(s), however, is a crucial factor for therapeutic success. Based on homology modeling, we previously identified four amino acids in the active site of Rho-kinase that likely determine inhibitor specificities observed for Rho-kinase relative to protein kinase A (PKA) (in PKA numbering: T183A, L49I, V123M, and E127D), and a fifth (Q181K) that played a surprising role in PKA-PKB hybrid proteins. We have systematically mutated these residues in PKA to their counterparts in Rho-kinase, individually and in combination. Using four Rho-kinase-specific, one PKA-specific, and one pan-kinase-specific inhibitor, we measured the inhibitor-binding properties of the mutated proteins and identify the roles of individual residues as specificity determinants. Two combined mutant proteins, containing the combination of mutations T183A and L49I, closely mimic Rho-kinase. Kinetic results corroborate the hypothesis that side-chain identities form the major determinants of selectivity. An unexpected result of the analysis is the consistent contribution of the individual mutations by simple factors. Crystal structures of the surrogate kinase inhibitor complexes provide a detailed basis for an understanding of these selectivity determinant residues. The ability to obtain kinetic and structural data from these PKA mutants, combined with their Rho-kinase-like selectivity profiles, make them valuable for use as surrogate kinases for structure-based inhibitor design.
-{{STRUCTURE_2gng|  PDB=2gng  |  SCENE=  }}
+Structural analysis of protein kinase A mutants with Rho-kinase inhibitor specificity.,Bonn S, Herrero S, Breitenlechner CB, Erlbruch A, Lehmann W, Engh RA, Gassel M, Bossemeyer D J Biol Chem. 2006 Aug 25;281(34):24818-30. Epub 2006 May 12. PMID:16699172<ref>PMID:16699172</ref>
-===Protein kinase A fivefold mutant model of Rho-kinase===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_16699172}}
-==About this Structure==
-[[2gng]] is a 2 chain structure with sequence 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=2GNG OCA].
 ==See Also==
 *[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:016699172</ref><ref group="xtra">PMID:014656443</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Bos taurus]]
 [[Category: CAMP-dependent protein kinase]]