1p35

CRYSTAL STRUCTURE OF BACULOVIRUS P35

spinqualitylabelsall models 1p35, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1p35 is a 3 chain structure with sequence from Acmnpv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [VP35_NPVAC] Blocks the insect or worm host cells apoptotic response initiated by the viral infection. Confers protection from cell death in mammalian cells. Acts by blocking the activity of members of the caspase family of proteases. Required for late and very late gene expression. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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