title: Structures of five mutants of toxic shock syndrome toxin-1 with reduced biological activity.
abstract: The three-dimensional structures of five mutants of toxic shock syndrome toxin-1 (TSST-1) have been determined. These mutations are in the long central alpha helix and are useful in mapping portions of TSST-1 involved in superantigenicity and lethality. The T128A, H135A, Q139K, and I140T mutations appear to reduce superantigenicity by altering the properties of the T-cell receptor interaction surface. The Q136A mutation is at a largely buried site and causes a dramatic change in the conformation of the beta7-beta9 loop which covers the back of the central alpha helix. As this mutation has the unique ability to reduce the toxin's lethality in rabbits while retaining its superantigenicity, it raises the possibility that this rear loop mediates the ability of TSST-1 to induce lethality and suggests a route for producing nonlethal toxins for therapeutic development.
authors.affiliation: Department of Biochemistry, Medical School, University of Minnesota, Minneapolis 55455, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Earhart
authors.forename: D T
authors.initials: DT
authors.lastname: Mitchell
authors.forename: D L
authors.initials: DL
authors.lastname: Murray
authors.forename: D M
authors.initials: DM
authors.lastname: Pinheiro
authors.forename: M
authors.initials: M
authors.lastname: Matsumura
authors.forename: P M
authors.initials: PM
authors.lastname: Schlievert
authors.forename: D H
authors.initials: DH
authors.lastname: Ohlendorf
mesh_terms: D000409:Alanine / Q000235:genetics; D000818:Animals; D001427:Bacterial Toxins; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry* / Q000235:genetics* / Q000633:toxicity; D005973:Glutamine / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011817:Rabbits; D013211:Staphylococcus aureus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018089:Superantigens / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D013912:Threonine / Q000235:genetics
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D005973:Glutamine; D013912:Threonine; D006639:Histidine; D008239:Lysine; D000409:Alanine