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3bok

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Revision as of 08:35, 9 February 2016

Structure of the C. botulinum neurotoxin serotype A apo-enzyme

Structural highlights

3bok is a 1 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3bon, 3boo
Gene:	BOTA, ATX, BNA (Clostridium botulinum)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The Clostridium botulinum neurotoxin serotype A light chain (BoNT/A-LC) is a Zn(II)-dependent metalloprotease that blocks the release of acetylcholine at the neuromuscular junction by cleaving SNAP-25, one of the SNARE proteins required for exocytosis. Because of the potential for use of the toxin in bioterrorism and the increasingly widespread application of the toxin in the medical field, there is significant interest in the development of small-molecule inhibitors of the metalloprotease. Efforts to design such inhibitors have not benefited from knowledge of how peptides bind to the active site since the enzyme-peptide structures available previously either were not occupied in the vicinity of the catalytic Zn(II) ion or did not represent the product of SNAP-25 substrate cleavage. Herein we report the 1.4 A-resolution X-ray crystal structure of a complex between the BoNT/A-LC and the inhibitory peptide N-Ac-CRATKML, the first structure of the light chain with an inhibitory peptide bound at the catalytic Zn(II) ion. The peptide is bound with the Cys S gamma atom coordinating the metal ion. Surprisingly, the cysteine sulfur is oxidized to the sulfenic acid form. Given the unstable nature of this species in solution, is it likely that oxidation occurs on the enzyme. In addition to the peptide-bound structure, we report two structures of the unliganded light chain with and without the Zn(II) cofactor bound at 1.25 and 1.20 A resolution, respectively. The two structures are nearly identical, confirming that the Zn(II) ion plays a purely catalytic role. Additionally, the structure of the Zn(II)-bound uncomplexed enzyme allows identification of the catalytic water molecule and a second water molecule that occupies the same position as the peptidic oxygen in the tetrahedral intermediate. This observation suggests that the enzyme active site is prearranged to stabilize the tetrahedral intermediate of the protease reaction.

Catalytic features of the botulinum neurotoxin a light chain revealed by high resolution structure of an inhibitory peptide complex.,Silvaggi NR, Wilson D, Tzipori S, Allen KN Biochemistry. 2008 May 27;47(21):5736-45. Epub 2008 May 6. PMID:18457419^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Silvaggi NR, Wilson D, Tzipori S, Allen KN. Catalytic features of the botulinum neurotoxin a light chain revealed by high resolution structure of an inhibitory peptide complex. Biochemistry. 2008 May 27;47(21):5736-45. Epub 2008 May 6. PMID:18457419 doi:10.1021/bi8001067

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3bok"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bon|3bon]], [[3boo|3boo]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BOTA, ATX, BNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bok OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bok RCSB], [http://www.ebi.ac.uk/pdbsum/3bok PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bok OCA], [http://pdbe.org/3bok PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bok RCSB], [http://www.ebi.ac.uk/pdbsum/3bok PDBsum]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 15: / Line 15: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bok ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 25: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3bok" style="background-color:#fffaf0;"></div>
 ==See Also==

3bok

From Proteopedia

Revision as of 08:35, 9 February 2016

Structure of the C. botulinum neurotoxin serotype A apo-enzyme

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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