2g7q
From Proteopedia
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|PDB= 2g7q |SIZE=350|CAPTION= <scene name='initialview01'>2g7q</scene>, resolution 2.41Å | |PDB= 2g7q |SIZE=350|CAPTION= <scene name='initialview01'>2g7q</scene>, resolution 2.41Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=AHL:N-HYDROXY-L-ARGININAMIDE'>AHL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [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] | + | |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> |
|GENE= botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum]) | |GENE= botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2g7n|2G7N]], [[2g7k|2G7K]], [[2g7p|2G7P]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g7q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g7q OCA], [http://www.ebi.ac.uk/pdbsum/2g7q PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2g7q RCSB]</span> | ||
}} | }} | ||
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[[Category: Janda, K D.]] | [[Category: Janda, K D.]] | ||
[[Category: Kim, J J.P.]] | [[Category: Kim, J J.P.]] | ||
| - | [[Category: AHL]] | ||
| - | [[Category: ZN]] | ||
[[Category: botulinum neurotoxin]] | [[Category: botulinum neurotoxin]] | ||
[[Category: snap25]] | [[Category: snap25]] | ||
[[Category: zinc protease]] | [[Category: zinc protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:12:57 2008'' |
Revision as of 00:12, 31 March 2008
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| , resolution 2.41Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | botA, atx, bna (Clostridium botulinum) | ||||||
| Activity: | Bontoxilysin, with EC number 3.4.24.69 | ||||||
| Related: | 2G7N, 2G7K, 2G7P
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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.
About this Structure
2G7Q 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
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