STRUCTURAL CHARACTERIZATIONS OF PROTEINS IN AN ANTIBIOTIC BIOSYNTHESIS PATHWAY USING SMALL ANGLE X-RAY SCATTERING AND X-RAY CRYSTALLOGRAPHY

Abstract

Tropodithietic acid (TDA) is an antibiotic with no known bacterial resistance\(^{1}\) and potential anticancer activity.\(^{2}\) Given that antibiotic resistance is a global crisis today, this antibiotic has significant health implications.\(^{3}\) TDA is a natural product that is synthesized by marine bacteria, for which the biosynthetic mechanism is not yet fully understood.\(^{4}\) Given the medicinal implications of TDA, a structural investigation into its biosynthetic proteins is critical for ultimately understanding the mechanism of synthesis. In this study, X-ray crystallography and small angle X-ray scattering were used to analyze the structures of four of the enzymes involved in TDA biosynthesis: TdaB, TdaC, TdaD, and TdaF. TdaD was determined to be a tetramer with binding sites located on the outside of the structure. This identification has implications for the TdaD putative active sites and can be used in further experiments for antibiotic studies.