Crystallographic Snapshots of Adenosyl Radical Enzymes

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

Reactions catalyzed by radical enzymes are essential for life processes. These include DNA repair, metabolism, catabolism, photosynthesis, as well as the biosynthesis of vitamins, cofactors, prostaglandins, antibiotics, and deoxynucleotides. An understanding of the mechanism of radical generation and radical-based catalysis, therefore, has applications in medicine and biotechnology. In this project, the Drennan laboratory will use X-ray crystallography as the chief tool to study the structure and mechanism of adenosylmethionine (AdoMet) and adenosylcobalamin (AdoCbl) radical enzymes. This research will go beyond the single picture of one enzyme from one organism, to analyze members of protein superfamilies and capture "snapshots" of enzymes as they proceed through their reaction pathways, allowing us to acquire fundamental information about radical-based reaction mechanisms. Through this research undergraduates, graduate students, and postdoctoral fellows will be trained in interdisciplinary areas of study. The Drennan laboratory currently consists of three postdoctoral scholars, nine graduate students, and three undergraduates, 67% of whom are female and 20% of whom are from under-represented minority groups. Broader impact activities include: incorporation of research examples into a freshmen chemistry course; development of an undergraduate association for MIT students interested in Biochemistry (in the absence of a biochemistry major); academic and research mentoring of undergraduate students; participation as both an MSRP research mentor and CONVERGE admissions officer (two programs geared toward recruitment of minority students to MIT); faculty advisor for the Women in Chemistry group; organizer of chemistry component of MIT-sponsored high school teachers training workshop; departmental mediator (resolving conflicts concerning graduate students); international education outreach through involvement with the US National Committee for the International Union of Biochemistry and Molecular Biology.