1ol6: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
|SITE= <scene name='pdbsite=AC1:Atp+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Atp+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene> | |LIGAND= <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/ | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ol6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ol6 OCA], [http://www.ebi.ac.uk/pdbsum/1ol6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ol6 RCSB]</span> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It is activated by phosphorylation and by the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation. In the absence of TPX2, the Aurora-A activation segment is in an inactive conformation, with the crucial phosphothreonine exposed and accessible for deactivation. Binding of TPX2 triggers no global conformational changes in the kinase but pulls on the activation segment, swinging the phosphothreonine into a buried position and locking the active conformation. The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation. | Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It is activated by phosphorylation and by the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation. In the absence of TPX2, the Aurora-A activation segment is in an inactive conformation, with the crucial phosphothreonine exposed and accessible for deactivation. Binding of TPX2 triggers no global conformational changes in the kinase but pulls on the activation segment, swinging the phosphothreonine into a buried position and locking the active conformation. The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation. | ||
==About this Structure== | ==About this Structure== | ||
| Line 24: | Line 24: | ||
Structural basis of Aurora-A activation by TPX2 at the mitotic spindle., Bayliss R, Sardon T, Vernos I, Conti E, Mol Cell. 2003 Oct;12(4):851-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14580337 14580337] | Structural basis of Aurora-A activation by TPX2 at the mitotic spindle., Bayliss R, Sardon T, Vernos I, Conti E, Mol Cell. 2003 Oct;12(4):851-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14580337 14580337] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | |||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bayliss, R.]] | [[Category: Bayliss, R.]] | ||
[[Category: Conti, E.]] | [[Category: Conti, E.]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: cell cycle]] | [[Category: cell cycle]] | ||
| Line 35: | Line 34: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:46:54 2008'' | ||