1P35

CRYSTAL STRUCTURE OF BACULOVIRUS P35

Summary for 1P35

• Entry DOI: 10.2210/pdb1p35/pdb
• Descriptor: P35, PHOSPHATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: apoptosis, p35, cell death, baculovirus
• Biological source: Autographa californica nucleopolyhedrovirus
• Total number of polymer chains: 3
• Total formula weight: 104911.73

Authors

Fisher, A.J.,Delacruz, W.P.,Zoog, S.J.,Schneider, C.L.,Friesen, P.D. (deposition date: 1998-09-18, release date: 1999-06-01, Last modification date: 2024-02-14)

Primary citation

Fisher, A.J.,Cruz, W.,Zoog, S.J.,Schneider, C.L.,Friesen, P.D.
Crystal structure of baculovirus P35: role of a novel reactive site loop in apoptotic caspase inhibition.
EMBO J., 18:2031-2039, 1999

PubMed Abstract: 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.

PubMed: 10205157
DOI: 10.1093/emboj/18.8.2031

Experimental method

X-RAY DIFFRACTION (2.2 Å)