Dave Stout's Lab

We use X-ray crystallography to determine the structure and function of membrane bound enzymes, and to enable drug design against cytochrome P450s and HIV protease.

Major effort is focused on transhydrogenase (TH), a mitochondrial enzyme and large integral membrane protein. Structure determination will elucidate the mechanism by which TH transduces the proton motive force generated by respiration into the chemistry required to maintain a reducing environment. Understanding of TH function is relevant to type 2 diabetes and neurodegenerative diseases.

Mitochondrial P450 enzymes catalyze highly specific reactions in the biosynthesis and degradation of hormones; CYP24A1 oxidizes the active form vitamin D, and therefore is an ideal target for inhibitor development to treat diseases inked to vitamin D insufficiency, including chronic kidney disease and cancer.

HIV protease (PR) is a proven target for drugs that suppress HIV AIDS, but treatment leads to multi-drug-resistant mutants. As a strategy to defeat the evolution of viral resistance, we are employing fragment based lead discovery to develop novel classes of allosteric PR inhibitors able to act in synergy with FDA approved drugs.

Scientific research is a community activity that involves interaction, collaboration, training and mentoring. To embrace the stimulation environment for learning and discovery at Scripps, our laboratory engages in a number of collaborative research projects. These provide a context for graduate students and postdoctoral fellows to share ideas, results, and techniques. Almost always, communication about overlapping interests and challenges leads to new insights and increases the excitement of doing research.