CYP24A1 and the Metabolism of Vitamin D

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CYP24A1 belongs to a class of enzymes called mitochondrial P450s, which catalyze specific reactions in the biosynthesis and degradation of hormones. CYP24A1 metabolizes vitamin D, which functions in calcium homeostasis and cellular growth processes. An overexpression of CYP24A1 in disease states may lead to bone disorders, kidney disease, and breast or prostate cancer. A potential treatment could be an inhibitor of CYP24A1. CYP24A1’s mechanism of action is poorly understood as it has been relatively difficult to crystallize. As a membrane protein, CYP24A1 has extensive hydrophobic regions, making this process more difficult. The Stout Lab recently overcame this challenge and solved the first crystal structure for CYP24A1, but without vitamin D bound. Now that a structure of CYP24A1 has been determined, further understanding of enzyme function can be gained by solving structures with vitamin D and designed inhibitors bound in the active site. To assist in this effort the Lutheran High School of San Diego SMART Team (Students Modeling A Research Topic) used data from the Stout Lab to create a physical model of CYP24A1 using 3D printing technology. The model will be very useful in understanding the conformational changes that occur in this large complex protein structure upon vitamin D binding. Supported by grants from the HHMI Pre‐College Program, and Cytochroma, Inc. for research at TSRI.