PDBsum entry 4lgs

Hydrolase/immune system

PDB id: 4lgs

Contents

Protein chains

263 a.a.

129 a.a.

Waters ×18

PDB id:

4lgs

Name:

Hydrolase/immune system

Title:

Ricin a chain bound to camelid nanobody (vhh4)

Structure:

Ricin. Chain: a. Fragment: unp residues 39-301. Synonym: ricin a chain, rrna n-glycosidase. Engineered: yes. Camelid nanobody (vhh4). Chain: b. Engineered: yes

Source:

Ricinus communis. Castor bean. Organism_taxid: 3988. Expressed in: escherichia coli. Expression_system_taxid: 469008. Vicugna pacos. Organism_taxid: 30538.

Resolution:

2.70Å R-factor: 0.202 R-free: 0.248

Authors:

M.J.Rudolph,J.Cheung,M.Franklin,F.Burshteyn,M.Cassidy,E.Gary,N.Mantis

Key ref:

M.J.Rudolph et al. (2014). Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with neutralizing and non-neutralizing single-chain antibodies. J Mol Biol, 426, 3057-3068. PubMed id: 24907552 DOI: 10.1016/j.jmb.2014.05.026

Date:

28-Jun-13 Release date: 11-Jun-14

Protein chain

P02879  (RICI_RICCO) -  Ricin from Ricinus communis

Seq: 576 a.a.

Struc: 263 a.a.

Protein chain

No UniProt id for this chain

Struc: 129 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.3.2.2.22 - rRNA N-glycosylase.
• Reaction: Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.

DOI no: 10.1016/j.jmb.2014.05.026

J Mol Biol 426:3057-3068 (2014)

PubMed id: 24907552

Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with neutralizing and non-neutralizing single-chain antibodies.

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.

ABSTRACT

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.