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| [[Image:1i3p.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1i3p| PDB=1i3p | SCENE= }} | | {{STRUCTURE_1i3p| PDB=1i3p | SCENE= }} |
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| '''THE 3.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF A MUTATED BACULOVIRUS P35 AFTER CASPASE CLEAVAGE'''
| | ===THE 3.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF A MUTATED BACULOVIRUS P35 AFTER CASPASE CLEAVAGE=== |
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| ==Overview==
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| Baculovirus P35 is a universal suppressor of apoptosis that stoichiometrically inhibits cellular caspases in a novel cleavage-dependent mechanism. Upon caspase cleavage at Asp-87, the 10- and 25-kDa cleavage products of P35 remain tightly associated with the inhibited caspase. Mutations in the alpha-helix of the reactive site loop preceding the cleavage site abrogate caspase inhibition and antiapoptotic activity. Substitution of Pro for Val-71, which is located in the middle of this alpha-helix, produces a protein that is cleaved at the requisite Asp-87 but does not remain bound to the caspase. This loss-of-function mutation provided the opportunity to structurally analyze the conformational changes of the P35 reactive site loop after caspase cleavage. We report here the 2.7 A resolution crystal structure of V71P-mutated P35 after cleavage by human caspase-3. The structure reveals a large movement in the carboxyl-terminal side of the reactive site loop that swings down and forms a new beta-strand that augments an existing beta-sheet. Additionally, the hydrophobic amino terminus releases and extends away from the protein core. Similar movements occur when P35 forms an inhibitory complex with human caspase-8. These findings suggest that the alpha-helix mutation may alter the sequential steps or kinetics of the conformational changes required for inhibition, thereby causing P35 loss of function.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11402050}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11402050 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11402050}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Helix-turn-helix]] | | [[Category: Helix-turn-helix]] |
| [[Category: Reactive site loop]] | | [[Category: Reactive site loop]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:32:05 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:22:01 2008'' |
