Squire Booker is bringing to light how enzymes accelerate some of the most reluctant chemical transformations inside cells. What he is learning has opened up new opportunities to improve human health.
Booker is particularly interested in how enzymes use cofactors, such as metal clusters or simple metal ions, to increase their catalytic capabilities. His lab team is well known for its work with so-called radical S-adenosylmethionine enzymes – proteins that use iron-sulfur clusters to generate highly reactive molecules that, in turn, initiate a mind-boggling array of chemical reactions. Booker wants to elucidate the mechanism behind some of those reactions, including many involved in the synthesis of natural products with antibacterial or anticancer properties.
His team has also unraveled details of the enzyme-catalyzed reaction that attaches a chemical group called a methyl to bacterial RNA, a modification that makes the microbes resistant to several classes of antibiotics. Booker's team is now working to generate inhibitors of this reaction.