Abstract: How do microbes live on the pollutant carbon monoxide? How do microbes split the triple bond of nitrogen gas? How do microbes harness the reactivity of radical species to afford challenging chemistry such as the biosynthesis of natural products? When it comes to performing difficult chemical reactions, microbes often combine a protein scaffold with a highly reactive metallocofactor; they essentially employ the metallocofactor as a “hired gun.” The Drennan lab combines X-ray crystallography and cryo-electron microscopy with other biophysical methods to reveal the secrets behind metalloenzyme chemistry. In this seminar, Drennan will focus on her lab's use of cryo-EM to understand the protein design principles involved in harnessing radical species and controlling metal ion reactivity