Understanding proteins in their native environments and the full conformational landscapes they explore is essential for linking structure to function. This seminar focuses on lipoxygenases (LOXs), a family of non-heme, primarily iron-containing enzymes that catalyze the regio- and stereospecific oxygenation of polyunsaturated fatty acids (PUFAs) released from membranes by phospholipases. While phospholipases rely on membrane interfaces for activation, certain LOXs exhibit a remarkable duality: they remain active in soluble systems but demonstrate accelerated catalysis at lipid-water interfaces. This presentation will delve into the molecular basis of this “interfacial acceleration” across the LOX phylogeny, a critical knowledge gap in the field. By integrating evolutionary biochemistry, AI-driven structural predictions, advanced biophysical techniques, and crystal/cryo-EM structures, this work uncovers conserved mechanisms of LOX activation. Ultimately, the findings provide new insights into motion-based drug design targeting key human lipoxygenases.

Speaker Bio:

It is my pleasure to introduce Dr. Nathan Gilbert. He earned both his B.S. and Ph.D. at LSU, completing his doctoral research in Dr. Marcia Newcomer’s laboratory in 2011. Following his time at LSU, Nathan moved to Vanderbilt Medical Center, where, as a postdoctoral fellow in the laboratories of Dr. Tina Iverson and Dr. Rich Breyer, he explored G protein-coupled receptors involved in eicosanoid signaling, with a particular focus on prostaglandin E2 receptors. Nathan’s career path next led him into biotechnology, where he worked with a start-up company developing novel biophysical techniques for detecting protein-small molecule interactions. After recognizing the uncertainty facing the company, Nathan returned to Baton Rouge, accepting a position as Beamline Manager at the LSU Center for Advanced Microstructures and Devices (CAMD). His expertise and leadership soon earned him a promotion to research assistant professor, where he secured his own R15 grant to support his independent research. In August 2024, Nathan returned back to the campus of LSU in a new role as a tenure-track assistant professor in the Department of Biological Sciences, within the Biochemistry and Molecular Biology division. Nathan will now share his research interests and the techniques he utilizes to probe macromolecular interactions.