2fst: Difference between revisions
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[[Image:2fst.jpg|left|200px]] | [[Image:2fst.jpg|left|200px]] | ||
'''mitogen activated protein kinase p38alpha (D176A+F327L) activating mutant''' | {{Structure | ||
|PDB= 2fst |SIZE=350|CAPTION= <scene name='initialview01'>2fst</scene>, resolution 1.45Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene> | |||
|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] | |||
|GENE= | |||
}} | |||
'''mitogen activated protein kinase p38alpha (D176A+F327L) activating mutant''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2FST is a [ | 2FST is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FST OCA]. | ||
==Reference== | ==Reference== | ||
Structures of p38alpha active mutants reveal conformational changes in L16 loop that induce autophosphorylation and activation., Diskin R, Lebendiker M, Engelberg D, Livnah O, J Mol Biol. 2007 Jan 5;365(1):66-76. Epub 2006 Aug 22. PMID:[http:// | Structures of p38alpha active mutants reveal conformational changes in L16 loop that induce autophosphorylation and activation., Diskin R, Lebendiker M, Engelberg D, Livnah O, J Mol Biol. 2007 Jan 5;365(1):66-76. Epub 2006 Aug 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17059827 17059827] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
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[[Category: Livnah, O.]] | [[Category: Livnah, O.]] | ||
[[Category: BOG]] | [[Category: BOG]] | ||
[[Category: active | [[Category: active mutant]] | ||
[[Category: autophosphorylation]] | [[Category: autophosphorylation]] | ||
[[Category: | [[Category: lipid]] | ||
[[Category: map kinase insertion]] | [[Category: map kinase insertion]] | ||
[[Category: mitogen activated protein kinase]] | [[Category: mitogen activated protein kinase]] | ||
[[Category: p38]] | [[Category: p38]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:56:22 2008'' | ||
Revision as of 17:56, 20 March 2008
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| , resolution 1.45Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
mitogen activated protein kinase p38alpha (D176A+F327L) activating mutant
OverviewOverview
p38 mitogen-activated protein (MAP) kinases function in numerous signaling processes and are crucial for normal functions of cells and organisms. Abnormal p38 activity is associated with inflammatory diseases and cancers making the understanding of its activation mechanisms highly important. p38s are commonly activated by phosphorylation, catalyzed by MAP kinase kinases (MKKs). Moreover, it was recently revealed that the p38alpha is also activated via alternative pathways, which are MKK independent. The structural basis of p38 activation, especially in the alternative pathways, is mostly unknown. This lack of structural data hinders the study of p38's biology as well as the development of novel strategies for p38 inhibition. We have recently discovered and optimized a novel set of intrinsically active p38 mutants whose activities are independent of any upstream activation. The high-resolution crystal structures of the intrinsically active p38alpha mutants reveal that local alterations in the L16 loop region promote kinase activation. The L16 loop can be thus regarded as a molecular switch that upon conformational changes promotes activation. We suggest that similar conformational changes in L16 loop also occur in natural activation mechanisms of p38alpha in T-cells. Our biochemical studies reveal novel mechanistic insights into the activation process of p38. In this regard, the results indicate that the activation mechanism of the mutants involves dimerization and subsequent trans autophosphorylation on Thr180 (on the phosphorylation lip). Finally, we suggest a model of in vivo p38alpha activation induced by the L16 switch with auto regulatory characteristics.
About this StructureAbout this Structure
2FST is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structures of p38alpha active mutants reveal conformational changes in L16 loop that induce autophosphorylation and activation., Diskin R, Lebendiker M, Engelberg D, Livnah O, J Mol Biol. 2007 Jan 5;365(1):66-76. Epub 2006 Aug 22. PMID:17059827
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