6bvd

Structure of Botulinum Neurotoxin Serotype HA Light Chain

spinqualitylabelsall models 6bvd, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bvd is a 2 chain structure with sequence from "bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The extreme toxicity of botulinum neurotoxins (BoNTs) relies on their specific cleavage of SNARE proteins, which eventually leads to muscle paralysis. One newly identified mosaic toxin, BoNT/HA (aka H or FA), cleaves VAMP-2 at a unique position between residues L54 and E55, but the molecular basis underlying VAMP-2-recognition of BoNT/HA remains poorly characterized. Here, we report a approximately 2.09 A resolution crystal structure of the light chain protease domain of BoNT/HA (LC/HA). Structural comparison between LC/HA and LC of BoNT/F1 (LC/F1) reveals distinctive hydrophobic and electrostatic features near the active sites, which may explain their different VAMP-2 cleavage sites. When compared to BoNT/F5 that cleaves VAMP-2 at the same site as BoNT/HA, LC/HA displays higher affinity for VAMP-2, which could be caused by their different surface charge properties surrounding a VAMP-2 exosite-binding cleft. Furthermore, systematic mutagenesis studies on VAMP-2 and structural modeling demonstrate that residues R47 to K59 spanning the cleavage site in VAMP-2 may adopt a novel extended conformation when interacting with LC/HA and LC/F5. Taken together, our structure provides new insights into substrate-recognition of BoNT/HA and paves the way for rational design of small molecule or peptide inhibitors against LC/HA. Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA.,Lam KH, Sikorra S, Weisemann J, Maatsch H, Perry K, Rummel A, Binz T, Jin R Pathog Dis. 2018 Apr 23. pii: 4982781. doi: 10.1093/femspd/fty044. PMID:29688327 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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