1zn3
Crystal structure of Glu335Ala mutant of Clostridium botulinum neurotoxin type E
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OverviewOverview
Clostridial neurotoxins comprising the seven serotypes of botulinum, neurotoxins and tetanus neurotoxin are the most potent toxins known to, humans. Their potency coupled with their specificity and selectivity, underscores the importance in understanding their mechanism of action in, order to develop a strategy for designing counter measures against them., To develop an effective vaccine against the toxin, it is imperative to, achieve an inactive form of the protein which preserves the overall, conformation and immunogenicity. Inactive mutants can be achieved either, by targeting active site residues or by modifying the surface charges, farther away from the active site. The latter affects the long-range, forces such as electrostatic potentials in a subtle way without disturbing, the structural integrity of the toxin causing some drastic changes in the, activity/environment. Here we report structural and biochemical analysis, on several mutations on Clostridium botulinum neurotoxin type E light, chain with at least two producing dramatic effects: Glu335Gln causes the, toxin to transform into a persistent apoenzyme devoid of zinc, and, Tyr350Ala has no hydrolytic activity. The structural analysis of several, mutants has led to a better understanding of the catalytic mechanism of, this family of proteins. The residues forming the S1' subsite have been, identified by comparing this structure with a thermolysin-inhibitor, complex structure.
About this StructureAbout this Structure
1ZN3 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 Full crystallographic information is available from OCA.
ReferenceReference
Analysis of active site residues of botulinum neurotoxin E by mutational, functional, and structural studies: Glu335Gln is an apoenzyme., Agarwal R, Binz T, Swaminathan S, Biochemistry. 2005 Jun 14;44(23):8291-302. PMID:15938619
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