2ar9: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2ar9 |SIZE=350|CAPTION= <scene name='initialview01'>2ar9</scene>, resolution 2.8Å | |PDB= 2ar9 |SIZE=350|CAPTION= <scene name='initialview01'>2ar9</scene>, resolution 2.8Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=DMR:2-HYDROXY-SUCCINIC ACID'>DMR</scene> | |LIGAND= <scene name='pdbligand=DMR:2-HYDROXY-SUCCINIC+ACID'>DMR</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ar9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ar9 OCA], [http://www.ebi.ac.uk/pdbsum/2ar9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ar9 RCSB]</span> | |||
}} | }} | ||
| Line 28: | Line 31: | ||
[[Category: Shiozaki, E N.]] | [[Category: Shiozaki, E N.]] | ||
[[Category: Srinivassula, S M.]] | [[Category: Srinivassula, S M.]] | ||
[[Category: caspase]] | [[Category: caspase]] | ||
[[Category: caspase activation]] | [[Category: caspase activation]] | ||
| Line 35: | Line 37: | ||
[[Category: initiator caspase]] | [[Category: initiator caspase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:56:16 2008'' | ||
Revision as of 01:56, 31 March 2008
| |||||||
| , resolution 2.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of a dimeric caspase-9
OverviewOverview
Caspases are responsible for the execution of programmed cell death (apoptosis) and must undergo proteolytic activation, in response to apoptotic stimuli, to function. The mechanism of initiator caspase activation has been generalized by the induced proximity model, which is thought to drive dimerization-mediated activation of caspases. The initiator caspase, caspase-9, exists predominantly as a monomer in solution. To examine the induced proximity model, we engineered a constitutively dimeric caspase-9 by relieving steric hindrance at the dimer interface. Crystal structure of the engineered caspase-9 closely resembles that of the wild-type (WT) caspase-9, including all relevant structural details and the asymmetric nature of two monomers. Compared to the WT caspase-9, this engineered dimer exhibits a higher level of catalytic activity in vitro and induces more efficient cell death when expressed. However, the catalytic activity of the dimeric caspase-9 is only a small fraction of that for the Apaf-1-activated caspase-9. Furthermore, in contrast to the WT caspase-9, the activity of the dimeric caspase-9 can no longer be significantly enhanced in an Apaf-1-dependent manner. These findings suggest that dimerization of caspase-9 may be qualitatively different from its activation by Apaf-1, and in conjunction with other evidence, posit an induced conformation model for the activation of initiator caspases.
About this StructureAbout this Structure
2AR9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Engineering a dimeric caspase-9: a re-evaluation of the induced proximity model for caspase activation., Chao Y, Shiozaki EN, Srinivasula SM, Rigotti DJ, Fairman R, Shi Y, PLoS Biol. 2005 Jun;3(6):e183. Epub 2005 May 10. PMID:15941357
Page seeded by OCA on Mon Mar 31 01:56:16 2008