Structural analysis of ricin and implications for inhibitor design

Toxicon. 1996 Nov-Dec;34(11-12):1325-34. doi: 10.1016/s0041-0101(96)00103-1.

Abstract

Ricin is a potent cytotoxin with experimental and clinical uses; it has also been used as a poison. There is considerable interest in identifying or designing inhibitors of the toxin that could be administered as antidotes. The X-ray structure of ricin A-chain is known and a plausible mechanism of action has been proposed. This provides a structural and chemical framework around which inhibitors could be designed; such a structure-based project is underway. Computer programs such as DOCK, GRID, SYBYL, and CHEMX have been used to map the ricin A-chain binding site and to search for potential inhibitors. Inhibitor candidates can be assayed kinetically in a protein synthesis assay and binding can be observed crystallographically. Taken together, a workable search algorithm has been developed and initial tests indicate that at least one ricin A-chain inhibitor, pteroic acid, has been identified.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Crystallography, X-Ray
  • Drug Design*
  • Humans
  • Protein Engineering*
  • Ricin / antagonists & inhibitors*
  • Ricin / chemistry*
  • Software
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Ricin