Using structural biology to understand enzyme function: from natural product biosynthesis to complex carbohydrate metabolism

Abstract: Enzymes play critical roles in the construction and breakdown of complex organic molecules. There are several key questions when seeking to understand the function of an enzyme. What is its substrate? What is its mechanism of action? What are the mechanisms of resistance to known inhibitors? This seminar will describe three recent examples where structural biology was critical to elucidating enzyme function. First, crystallography was used to identify a disaccharide substrate for new glycoside hydrolases from the human gut microbiome. Second, the structure of an enzyme that catalyzes N-N bond formation in the biosynthesis of piperazic acid gives clues to its mechanism of action. Last, a unique mechanism of resistance to the antibiotic indolmycin was unveiled by determining the crystal structure of an indolmycin-resistant tryptophanyl-tRNA synthetase.