2a8a: Difference between revisions

Revision as of 18:44, 3 May 2008

Crystal structure of Clostridium botulinum neurotoxin serotype F light chain

OverviewOverview

The seven serologically distinct Clostridium botulinum neurotoxins (BoNTs A-G) are zinc endopeptidases which block the neurotransmitter release by cleaving one of the three proteins of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor complex (SNARE complex) essential for the fusion of vesicles containing neurotransmitters with target membranes. These metallopeptidases exhibit unique specificity for the substrates and peptide bonds they cleave. Development of countermeasures and therapeutics for BoNTs is a priority because of their extreme toxicity and potential misuse as biowarfare agents. Though they share sequence homology and structural similarity, the structural information on each one of them is required to understand the mechanism of action of all of them because of their specificity. Unraveling the mechanism will help in the ultimate goal of developing inhibitors as antibotulinum drugs for the toxins. Here, we report the high-resolution structure of active BoNT/F catalytic domain in two crystal forms. The structure was exploited for modeling the substrate binding and identifying the S1' subsite and the putative exosites which are different from BoNT/A or BoNT/B. The orientation of docking of the substrate at the active site is consistent with the experimental BoNT/A-LC:SNAP-25 peptide model and our proposed model for BoNT/E-LC:SNAP-25.

About this StructureAbout this Structure

2A8A is a Single protein structure of sequence from Clostridium botulinum. Full crystallographic information is available from OCA.

ReferenceReference

Structural analysis of botulinum neurotoxin serotype F light chain: implications on substrate binding and inhibitor design., Agarwal R, Binz T, Swaminathan S, Biochemistry. 2005 Sep 6;44(35):11758-65. PMID:16128577 Page seeded by OCA on Sat May 3 18:44:08 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:2a8a.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2a8a |SIZE=350|CAPTION= <scene name='initialview01'>2a8a</scene>, resolution 2.00&Aring;
+The line below this paragraph, containing "STRUCTURE_2a8a", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=CDA:First+Cd+Binding+Site'>CDA</scene>, <scene name='pdbsite=CDB:Second+Cd+Binding+Site'>CDB</scene> and <scene name='pdbsite=ZNB:Zn+Binding+Site'>ZNB</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= botF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum])
+-->
-|DOMAIN=
+{{STRUCTURE_2a8a|  PDB=2a8a  |  SCENE=  }}
-|RELATEDENTRY=[[2a97|2A97]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a8a OCA], [http://www.ebi.ac.uk/pdbsum/2a8a PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a8a RCSB]</span>
-}}
 '''Crystal structure of Clostridium botulinum neurotoxin serotype F light chain'''
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 [[Category: Binz, T.]]
 [[Category: Swaminathan, S.]]
-[[Category: botulinum neurotoxin serotype f]]
+[[Category: Botulinum neurotoxin serotype f]]
-[[Category: catalytic domain]]
+[[Category: Catalytic domain]]
-[[Category: x-ray]]
+[[Category: X-ray]]
-[[Category: zinc endopeptidase]]
+[[Category: Zinc endopeptidase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:44:08 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:49:09 2008''