This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2g7k

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2g7k.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2g7k.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2g7k| PDB=2g7k | SCENE= }}
{{STRUCTURE_2g7k| PDB=2g7k | SCENE= }}
-
'''Structure of the Light Chain of Botulinum Neurotoxin, Serotype A Bound to small Molecule Inhibitors'''
+
===Structure of the Light Chain of Botulinum Neurotoxin, Serotype A Bound to small Molecule Inhibitors===
-
==Overview==
+
<!--
-
Botulinum neurotoxin serotype A (BoNT/A, 1296 residues) is a zinc metalloprotease that cleaves SNAP25 to inhibit the fusion of neurotransmitter-carrying vesicles to the plasma membrane of peripheral neurons. BoNT/A is a disulfide-linked di-chain protein composed of an N-terminal, thermolysin-like metalloprotease light chain domain (LC/A, 448 residues) and a C-terminal heavy chain domain (848 residues) that can be divided into two subdomains, a translocation subdomain and a receptor binding subdomain. LC/A cleaves SNAP25 between residues Gln197-Arg198 and, unlike thermolysin, recognizes an extended region of SNAP25 for cleavage. The structure of a recombinant LC/A (1-425) treated with EDTA (No-Zn LC/A) was determined. The overall structure of No-Zn LC/A is similar to that reported for the holotoxin, except that it lacks the Zn ion, indicating that the role of Zn is catalytic not structural. In addition, structures of a noncatalytic mutant LC/A (Arg362Ala/Tyr365Phe) complexed with and without an inhibitor, ArgHX, were determined. The overall structure and the active site conformation for the mutant are the same as wild type. When the inhibitor binds to the active site, the carbonyl and N-hydroxyl groups form a bidentate ligand to the Zn ion and the arginine moiety binds to Asp369, suggesting that the inhibitor-bound structure mimics a catalytic intermediate with the Arg moiety binding at the P1' site. Consistent with this model, mutation of Asp369 to Ala decreases the catalytic activity of LC/A by approximately 600-fold, and the residual activity is not inhibited by ArgHX. These results provide new information on the reaction mechanism and insight into the development of strategies for small molecule inhibitors of BoNTs.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16846233}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16846233 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16846233}}
==About this Structure==
==About this Structure==
Line 33: Line 37:
[[Category: Snap25]]
[[Category: Snap25]]
[[Category: Zinc protease]]
[[Category: Zinc protease]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:46:59 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:09:23 2008''

Revision as of 10:09, 28 July 2008

Image:2g7k.png

Template:STRUCTURE 2g7k

Structure of the Light Chain of Botulinum Neurotoxin, Serotype A Bound to small Molecule Inhibitors

Template:ABSTRACT PUBMED 16846233

About this Structure

2G7K is a Single protein structure of sequence from Clostridium botulinum. Full crystallographic information is available from OCA.

Reference

Light chain of botulinum neurotoxin serotype A: structural resolution of a catalytic intermediate., Fu Z, Chen S, Baldwin MR, Boldt GE, Crawford A, Janda KD, Barbieri JT, Kim JJ, Biochemistry. 2006 Jul 25;45(29):8903-11. PMID:16846233

Page seeded by OCA on Mon Jul 28 13:09:23 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2g7k"
Personal tools