1t3c

Clostridium botulinum type E catalytic domain E212Q mutant

spinqualitylabelsall models 1t3c, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1t3c is a 2 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: CL, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BXE_CLOBO Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the 180-Arg-|-Ile-181 bond in SNAP-25. 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 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Botulinum neurotoxin 3D structures

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