1t3c
Clostridium botulinum type E catalytic domain E212Q mutant
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OverviewOverview
The seven serotypes of botulinum neurotoxins (A-G) produced by Clostridium, botulinum share significant sequence homology and structural similarity., The functions of their individual domains and the modes of action are also, similar. However, the substrate specificity and the peptide bond cleavage, selectivity of their catalytic domains are different. The reason for this, unique specificity of botulinum neurotoxins is still baffling. If an, inhibitor leading to a therapeutic drug common to all serotypes is to be, developed, it is essential to understand the differences in their, three-dimensional structures that empower them with this unique, characteristic. Accordingly, high-resolution structures of all serotypes, are required, and toward achieving this goal the crystal structure of the, catalytic domain of C. botulinum neurotoxin type E has been determined to, 2.1 A resolution. The crystal structure of the inactive mutant, Glu212-->Gln of this protein has also been determined. While the overall, conformation is unaltered in the active site, the position of the, nucleophilic water changes in the mutant, thereby causing it to lose its, ability to activate the catalytic reaction. The structure explains the, importance of the nucleophilic water and the charge on Glu212. The, structural differences responsible for the loss of activity of the mutant, provide a common model for the catalytic pathway of Clostridium, neurotoxins since Glu212 is conserved and has a similar role in all, serotypes. This or a more nonconservative mutant (e.g., Glu212-->Ala), could provide a novel, genetically modified protein vaccine for botulinum.
About this StructureAbout this Structure
1T3C is a Single protein structure of sequence from Clostridium botulinum with ZN and CL as ligands. Active as Bontoxilysin, with EC number 3.4.24.69 Structure known Active Sites: AC1 and AC2. Full crystallographic information is available from OCA.
ReferenceReference
Structural analysis of botulinum neurotoxin type E catalytic domain and its mutant Glu212-->Gln reveals the pivotal role of the Glu212 carboxylate in the catalytic pathway., Agarwal R, Eswaramoorthy S, Kumaran D, Binz T, Swaminathan S, Biochemistry. 2004 Jun 1;43(21):6637-44. PMID:15157097
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