2fun: Difference between revisions

Revision as of 04:19, 4 May 2008

alternative p35-caspase-8 complex

OverviewOverview

Wide-spectrum caspase inhibition by the baculoviral p35 protein was previously shown to be a consequence of covalent inhibition in which a thioester bond is stably formed between the cleavage residue Asp87 of p35 and the active site Cys360' of caspase-8. Here we show that the N-terminal fragment of cleaved p35 (p35-N) is a circular peptide when dissociated from the caspase. Biochemical and crystallographic data suggest that p35-N circularization results from the trapping of a native chemical ligation intermediate in the p35/caspase complex, in which the N-terminal Cys2 of p35 attacks the Asp87-Cys360' thioester to form an equilibrium between Asp87-Cys2 and Asp87-Cys360'. This provides a crucial covalent interaction for keeping the N terminus of p35 bound in the caspase active site, which explains the absolute requirement of Cys2 for caspase inhibition. Participation of native chemical ligation in caspase inhibition by p35 illustrates an unusual mechanism of protease inhibition.

About this StructureAbout this Structure

2FUN is a Protein complex structure of sequences from Autographa californica nucleopolyhedrovirus and Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Native chemical ligation in covalent caspase inhibition by p35., Lu M, Min T, Eliezer D, Wu H, Chem Biol. 2006 Feb;13(2):117-22. PMID:16492559 Page seeded by OCA on Sun May 4 04:19:44 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2fun.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2fun |SIZE=350|CAPTION= <scene name='initialview01'>2fun</scene>, resolution 3.0&Aring;
+The line below this paragraph, containing "STRUCTURE_2fun", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND=
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE= P35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=46015 Autographa californica nucleopolyhedrovirus])
+-->
-|DOMAIN=
+{{STRUCTURE_2fun|  PDB=2fun  |  SCENE=  }}
-|RELATEDENTRY=[[1i4e|1I4E]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fun OCA], [http://www.ebi.ac.uk/pdbsum/2fun PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fun RCSB]</span>
-}}
 '''alternative p35-caspase-8 complex'''
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 [[Category: Min, T.]]
 [[Category: Wu, H.]]
-[[Category: apoptosis/hydrolase]]
+[[Category: Apoptosis/hydrolase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 04:19:44 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:07:55 2008''