Project Areas

Project Area: Understanding Vitamin-D metabolism

We seek to use a combination of biochemistry and biophysical techniques to understand the structural biology of vitamin-D metabolism. Vitamin-D is converted into its active form, 1,25(OH)2D3, by a series of cytochrome P450 enzymes. In turn, vitamin-D inactivation is mediated by another cytochrome P450 enzyme, CYP24A1. Our research in this area focuses on 1) the mode of substrate recognition for enzymes involved in this pathway, and 2) protein-protein interactions with the accessory protein Adrenodoxin. In recent work, we demonstrate that substrate recognition and Adrenodoxin binding, which represent the first two steps in the P450 reaction cycle, are structurally linked.

Project Area: CYP121 of Mycobacterium tuberculosis

The enzyme CYP121 is essential for the bacterium that causes Tuberculosis. CYP121 mediates an unusual phenol-coupling reaction on the dipeptide dicyclotyrosine. Here we aim to understand CYP121 function by studying changes in protein conformation. We recently demonstrated that the enzyme relies on formation of dimers to appropriately binding its substrate, and therefore to perform catalysis. This project was also the first reported use of 19F-NMR to study cytochrome P450 structure.