1p35

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{{Structure
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p35 OCA], [http://www.ebi.ac.uk/pdbsum/1p35 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1p35 RCSB]</span>
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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.]]
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[[Category: apoptosis]]
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[[Category: Apoptosis]]
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[[Category: baculovirus]]
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[[Category: Baculovirus]]
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[[Category: cell death]]
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[[Category: Cell death]]
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[[Category: p35]]
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[[Category: P35]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:37:26 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:54:09 2008''
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Revision as of 01:37, 3 May 2008

Template:STRUCTURE 1p35

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

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