title: Elucidation of the Covalent and Tertiary Structures of Biologically Active Ts3 Toxin.
abstract: Ts3 is an alpha scorpion toxin from the venom of the Brazilian scorpion Tityus serrulatus. Ts3 binds to the domain IV voltage sensor of voltage-gated sodium channels (Nav ) and slows down their fast inactivation. The covalent structure of the Ts3 toxin is uncertain, and the structure of the folded protein molecule is unknown. Herein, we report the total chemical synthesis of four candidate Ts3 toxin protein molecules and the results of structure-activity studies that enabled us to establish the covalent structure of biologically active Ts3 toxin. We also report the synthesis of the mirror image form of the Ts3 protein molecule, and the use of racemic protein crystallography to determine the folded (tertiary) structure of biologically active Ts3 toxin by X-ray diffraction.
authors.affiliation: Department of Chemistry, University of Chicago, Chicago, IL, 60637, USA.|Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL, 60637, USA.|Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Bobo
authors.initials: B
authors.lastname: Dang
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Department of Chemistry, University of Chicago, Chicago, IL, 60637, USA.|Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL, 60637, USA.|Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Kalyaneswar
authors.initials: K
authors.lastname: Mandal
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Correa
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL, 60637, USA.|Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bezanilla
authors.affiliation: Department of Chemistry, University of Chicago, Chicago, IL, 60637, USA. skent@uchicago.edu.|Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL, 60637, USA. skent@uchicago.edu.|Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, 60637, USA. skent@uchicago.edu.
authors.forename: Stephen B H
authors.initials: SB
authors.lastname: Kent
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012604:Scorpion Venoms / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D012605:Scorpions / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D062553:NAV1.4 Voltage-Gated Sodium Channel; D011994:Recombinant Proteins; D012604:Scorpion Venoms
keywords: X-ray crystallography; chemical protein synthesis; protein structures; proteins; toxins