Mani Larijani - March 29, 2021

Evolutionary comparative studies of DNA-editing enzymes: towards describing biological molecules as 5-dimensional beings

How do we describe the shape of a molecule? Biologists would answer this question with a description according to the centuries-old classic Euclidean geometry, which defines all shapes in 3-dimensional (3D) space. Our group studies the biochemical behaviors, biological functions, molecular structures, and evolution of enzymes that mutate DNA. These enzymes are involved in innate and adaptive immunity, as well as in cancer genesis and progression. The enzymes that we study have proved especially challenging for conventional 3D structure resolution by crystallography or NMR. To overcome these challenges, we developed a novel pipeline for structure determination, which involves computational, evolutionary and biochemical methods. I will present how our novel approach has not only contributed to solving 3D structures but has led us down a path of thinking about the concept of biological structures as 5-dimensional (5D) rather than 3D entities.