Chem & Biochem Collab: How a tiny enzyme helps build a big brain

Proposed mechanism of the C-terminal tail-regulated radical initiation. The dashed lines indicate H-bonding or electrostatic interactions between the Gating loop and the C-term tail or the adenine base of SAM.

Many enzymes use radical chemistry to build essential molecules, but radicals are highly reactive and can easily cause damage if not tightly controlled. The study by the labs of Profs. Ken Yokoyama, Pei Zhou, and Weitao Yang of the Chemistry Department reveals how a radical-generating enzyme, MoaA, from the radical S-adenosyl-L-methionine (SAM) superfamily, senses when its correct substrate is bound and safely triggers the radical reaction. Using a combination of nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy, computational modeling, and biochemical experiments, the researchers show how this mechanism prevents unwanted side reactions and provides insight into a human metabolic disease caused by related mutations. Learn more about this research in a recent edition of PNAS, available here.