1p35
From Proteopedia
(New page: 200px<br /><applet load="1p35" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p35, resolution 2.20Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1p35.gif|left|200px]]<br /><applet load="1p35" size=" | + | [[Image:1p35.gif|left|200px]]<br /><applet load="1p35" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1p35, resolution 2.20Å" /> | caption="1p35, resolution 2.20Å" /> | ||
'''CRYSTAL STRUCTURE OF BACULOVIRUS P35'''<br /> | '''CRYSTAL STRUCTURE OF BACULOVIRUS P35'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The aspartate-specific caspases are critical protease effectors of | + | 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== | ==About this Structure== | ||
| - | 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 PO4 and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: Autographa californica nucleopolyhedrovirus]] | [[Category: Autographa californica nucleopolyhedrovirus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Delacruz, W | + | [[Category: Delacruz, W P.]] |
| - | [[Category: Fisher, A | + | [[Category: Fisher, A J.]] |
| - | [[Category: Friesen, P | + | [[Category: Friesen, P D.]] |
| - | [[Category: Schneider, C | + | [[Category: Schneider, C L.]] |
| - | [[Category: Zoog, S | + | [[Category: Zoog, S J.]] |
[[Category: EDO]] | [[Category: EDO]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
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[[Category: p35]] | [[Category: p35]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:24:35 2008'' |
Revision as of 12:24, 21 February 2008
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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 and 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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