1p35
From Proteopedia
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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 with PO4 and EDO as ligands. 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
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