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1p35
From Proteopedia
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[[Image:1p35.gif|left|200px]] | [[Image:1p35.gif|left|200px]] | ||
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'''CRYSTAL STRUCTURE OF BACULOVIRUS P35''' | '''CRYSTAL STRUCTURE OF BACULOVIRUS P35''' | ||
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[[Category: Schneider, C L.]] | [[Category: Schneider, C L.]] | ||
[[Category: Zoog, S J.]] | [[Category: Zoog, S J.]] | ||
| - | [[Category: | + | [[Category: Apoptosis]] |
| - | [[Category: | + | [[Category: Baculovirus]] |
| - | [[Category: | + | [[Category: Cell death]] |
| - | [[Category: | + | [[Category: P35]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:37:26 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 01:37, 3 May 2008
CRYSTAL STRUCTURE OF BACULOVIRUS P35
Overview
The aspartate-specific caspases are critical protease effectors of programmed cell death and consequently represent important targets for apoptotic intervention. Baculovirus P35 is a potent substrate inhibitor of metazoan caspases, a property that accounts for its unique effectiveness in preventing apoptosis in phylogenetically diverse organisms. Here we report the 2.2 A resolution crystal structure of P35, the first structure of a protein inhibitor of the death caspases. The P35 monomer possesses a solvent-exposed loop that projects from the protein's main beta-sheet core and positions the requisite aspartate cleavage site at the loop's apex. Distortion or destabilization of this reactive site loop by site-directed mutagenesis converted P35 to an efficient substrate which, unlike wild-type P35, failed to interact stably with the target caspase or block protease activity. Thus, cleavage alone is insufficient for caspase inhibition. These data are consistent with a new model wherein the P35 reactive site loop participates in a unique multi-step mechanism in which the spatial orientation of the loop with respect to the P35 core determines post-cleavage association and stoichiometric inhibition of target caspases.
About this Structure
1P35 is a Single protein structure of sequence from Autographa californica nucleopolyhedrovirus. Full crystallographic information is available from OCA.
Reference
Crystal structure of baculovirus P35: role of a novel reactive site loop in apoptotic caspase inhibition., Fisher AJ, Cruz W, Zoog SJ, Schneider CL, Friesen PD, EMBO J. 1999 Apr 15;18(8):2031-9. PMID:10205157 Page seeded by OCA on Sat May 3 04:37:26 2008
