1p35: Difference between revisions

[[Image:1p35.gif|left|200px]]<br /><applet load="1p35" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1P35 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Autographa_californica_nucleopolyhedrovirus Autographa californica nucleopolyhedrovirus] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P35 OCA].  

[[Category: Delacruz, W P.]]

[[Category: Fisher, A J.]]

[[Category: Friesen, P D.]]

[[Category: Schneider, C L.]]

[[Category: Zoog, S J.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:24:35 2008''