title: Structural analysis of ricin and implications for inhibitor design.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas, Austin 78712, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Robertus
authors.forename: X
authors.initials: X
authors.lastname: Yan
authors.forename: S
authors.initials: S
authors.lastname: Ernst
authors.forename: A
authors.initials: A
authors.lastname: Monzingo
authors.forename: S
authors.initials: S
authors.lastname: Worley
authors.forename: P
authors.initials: P
authors.lastname: Day
authors.forename: T
authors.initials: T
authors.lastname: Hollis
authors.forename: M
authors.initials: M
authors.lastname: Svinth
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D015202:Protein Engineering; D012276:Ricin / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D012984:Software; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D012276:Ricin