View source for 4loo

==Structural basis of autoactivation of p38 alpha induced by TAB1 (Monoclinic crystal form)==
<StructureSection load='4loo' size='340' side='right' caption='[[4loo]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4loo]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LOO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LOO FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SB4:4-(4-FLUOROPHENYL)-1-(4-PIPERIDINYL)-5-(2-AMINO-4-PYRIMIDINYL)-IMIDAZOLE'>SB4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK14, Crk1, Csbp1, Csbp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=4loo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4loo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4loo RCSB], [http://www.ebi.ac.uk/pdbsum/4loo PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
p38alpha mitogen-activated protein kinase (p38alpha) is activated by a variety of mechanisms, including autophosphorylation initiated by TGFbeta-activated kinase 1 binding protein 1 (TAB1) during myocardial ischemia and other stresses. Chemical-genetic approaches and coexpression in mammalian, bacterial and cell-free systems revealed that mouse p38alpha autophosphorylation occurs in cis by direct interaction with TAB1(371-416). In isolated rat cardiac myocytes and perfused mouse hearts, TAT-TAB1(371-416) rapidly activates p38 and profoundly perturbs function. Crystal structures and characterization in solution revealed a bipartite docking site for TAB1 in the p38alpha C-terminal kinase lobe. TAB1 binding stabilizes active p38alpha and induces rearrangements within the activation segment by helical extension of the Thr-Gly-Tyr motif, allowing autophosphorylation in cis. Interference with p38alpha recognition by TAB1 abolishes its cardiac toxicity. Such intervention could potentially circumvent the drawbacks of clinical pharmacological inhibitors of p38 catalytic activity.

Mechanism and consequence of the autoactivation of p38alpha mitogen-activated protein kinase promoted by TAB1.,De Nicola GF, Martin ED, Chaikuad A, Bassi R, Clark J, Martino L, Verma S, Sicard P, Tata R, Atkinson RA, Knapp S, Conte MR, Marber MS Nat Struct Mol Biol. 2013 Sep 15. doi: 10.1038/nsmb.2668. PMID:24037507<ref>PMID:24037507</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Mitogen-activated protein kinase]]
[[Category: Mus musculus]]
[[Category: Allerston, C K]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Chaikuad, A]]
[[Category: DeNicola, G F]]
[[Category: Delft, F von]]
[[Category: Edwards, A M]]
[[Category: Knapp, S]]
[[Category: Krojer, T]]
[[Category: Marber, M S]]
[[Category: Structural genomic]]
[[Category: Autoactivation]]
[[Category: Autophosphorylation]]
[[Category: Kinase-regulatory protein complex]]
[[Category: Mapk]]
[[Category: Protein kinase]]
[[Category: Sgc]]
[[Category: Transferase]]