6cwk | pdb_00006cwk

Anti-RTA VHH antibody

spinqualitylabelsall models 6cwk, resolution 1.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6cwk is a 1 chain structure with sequence from Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.256Å Ligands: CL, EDO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Ricin toxin's enzymatic subunit (RTA) has been subjected to intensive B cell epitope mapping studies using a combination of competition ELISAs, hydrogen exchange-mass spectrometry and X-ray crystallography. Those studies identified four spatially distinct clusters (I-IV) of toxin-neutralizing epitopes on the surface of RTA. Here we describe A9, a new single domain camelid antibody (VHH) that was proposed to recognize a novel epitope on RTA that straddles clusters I and III. The X-ray crystal structure of A9 bound to RTA (2.6 A resolution) revealed extensive antibody contact with RTA's beta-strand h (732 A2 buried surface area; BSA), along with limited engagement with alpha-helix D (90 A2) and alpha-helix C (138 A2). Collectively, these contacts explain the overlap between epitope clusters I and III, as identified by competition ELISA. However, considerable binding affinity, and, consequently, toxin-neutralizing activity of A9 is mediated by an unusual CDR2 containing five consecutive Gly residues that interact with alpha-helix B (82 A2), a known neutralizing hotspot on RTA. Removal of a single Gly residue from the penta-glycine stretch in CDR2 reduced A9's binding affinity by 10-fold and eliminated toxin-neutralizing activity. Computational modeling indicates that removal of a Gly from CDR2 does not perturb contact with RTA per se, but results in the loss of an intramolecular hydrogen bond network involved in stabilizing CDR2 in the unbound state. These results reveal a novel configuration of a CDR2 element involved in neutralizing ricin toxin. Contribution of an unusual CDR2 element of a single domain antibody in ricin toxin binding affinity and neutralizing activity.,Rudolph MJ, Vance DJ, Kelow S, Angalakurthi SK, Nguyen S, Davis SA, Rong Y, Middaugh CR, Weis DD, Dunbrack R Jr, Karanicolas J, Mantis NJ Protein Eng Des Sel. 2018 Jul 1;31(7-8):277-287. doi: 10.1093/protein/gzy022. PMID:30265352 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures 3D structures of non-human antibody

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