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PDBsum entry 4lhq
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Hydrolase/immune system
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PDB id
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4lhq
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References listed in PDB file
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Key reference
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Title
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Crystal structures of ricin toxin'S enzymatic subunit (rta) in complex with neutralizing and non-Neutralizing single-Chain antibodies.
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Authors
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M.J.Rudolph,
D.J.Vance,
J.Cheung,
M.C.Franklin,
F.Burshteyn,
M.S.Cassidy,
E.N.Gary,
C.Herrera,
C.B.Shoemaker,
N.J.Mantis.
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Ref.
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J Mol Biol, 2014,
426,
3057-3068.
[DOI no: ]
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PubMed id
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Abstract
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Ricin is a select agent toxin and a member of the RNA N-glycosidase family of
medically important plant and bacterial ribosome-inactivating proteins. In this
study, we determined X-ray crystal structures of the enzymatic subunit of ricin
(RTA) in complex with the antigen binding domains (VHH) of five unique
single-chain monoclonal antibodies that differ in their respective
toxin-neutralizing activities. None of the VHHs made direct contact with
residues involved in RTA's RNA N-glycosidase activity or induced notable
allosteric changes in the toxin's subunit. Rather, the five VHHs had overlapping
structural epitopes on the surface of the toxin and differed in the degree to
which they made contact with prominent structural elements in two folding
domains of the RTA. In general, RTA interactions were influenced most by the VHH
CDR3 (CDR, complementarity-determining region) elements, with the most potent
neutralizing antibody having the shortest and most conformationally constrained
CDR3. These structures provide unique insights into the mechanisms underlying
toxin neutralization and provide critically important information required for
the rational design of ricin toxin subunit vaccines.
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