6OCA

Ricin A chain bound to VHH antibody V2G10

6OCA の概要

• エントリーDOI: 10.2210/pdb6oca/pdb
• 分子名称: Ricin A chain, VHH antibody V2G10, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: toxin
• 由来する生物種: Ricinus communis (Castor bean); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89768.73

構造登録者

Rudolph, M.J. (登録日: 2019-03-22, 公開日: 2020-04-01, 最終更新日: 2024-03-13)

主引用文献

Rudolph, M.J.,Czajka, T.F.,Davis, S.A.,Thi Nguyen, C.M.,Li, X.P.,Tumer, N.E.,Vance, D.J.,Mantis, N.J.
Intracellular Neutralization of Ricin Toxin by Single-domain Antibodies Targeting the Active Site.
J.Mol.Biol., 432:1109-1125, 2020

PubMed Abstract: The extreme potency of the plant toxin, ricin, is due to its enzymatic subunit, RTA, which inactivates mammalian ribosomes with near-perfect efficiency. Here we characterized, at the functional and structural levels, seven alpaca single-domain antibodies (VHs) previously reported to recognize epitopes in proximity to RTA's active site. Three of the VHs, V2A11, V8E6, and V2G10, were potent inhibitors of RTA in vitro and protected Vero cells from ricin when expressed as intracellular antibodies ("intrabodies"). Crystal structure analysis revealed that the complementarity-determining region 3 (CDR3) elements of V2A11 and V8E6 penetrate RTA's active site and interact with key catalytic residues. V2G10, by contrast, sits atop the enzymatic pocket and occludes substrate accessibility. The other four VHs also penetrated/occluded RTA's active site, but lacked sufficient binding affinities to outcompete RTA-ribosome interactions. Intracellular delivery of high-affinity, single-domain antibodies may offer a new avenue in the development of countermeasures against ricin toxin.toxin, antibody, structure, intracellular.

PubMed: 31931008
DOI: 10.1016/j.jmb.2020.01.006

実験手法

X-RAY DIFFRACTION (2.113 Å)