Authors:

Hillary English

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Human sulfotransferase (SULTs) is a supergene family that plays a very prominent role in detoxification. These enzymes catalyze reactions crucial to the human body. This process involves attaching a polar sulfate group to a molecule, increasing its water solubility, and thus causing its excretion. Recent evidence has brought to light that increased cholesterol sulfotransferase (SULT2B1b) activity leads to an imbalance of the cholesterol to sulfonated cholesterol homeostasis, which has been seen to lead to carcinogenesis in the human colon, prostate, and ovary tissues. Moreover, bioavailability of various drugs can be impaired by SULTs. SULT2B1 has two isoforms SULT2B1a and 1b, both members have enzymatic activity towards cholesterol. Recently, the Mesecar Lab, in collaboration with the Cooks Lab, developed a label-free high-throughput DESI-MS-based enzymatic assay, which serves as a platform for in-vitro inhibitor screening and dose-response inhibition studies. We have identified and validated several hit inhibitors from the screening for SULT2B1b. However, not a lot about SULT2B1a is known, and because it has a remarkably similar structure to SULT2B1b, the selectivity of these inhibitors/analogs between the two isoforms need to be explored. To do this, I have purified 2B1a in order to obtain structural information about the protein through X-ray crystallography, and have performed various inhibitor tests to see if compounds that bind to 2B1b might also bind to 2B1a. These experiments provide fundamental insights into what SULT 2B1a does, and will potentially prevent off-targeting effects of drugs meant to inhibit 2B1b. Keywords: Sulfotransferase; Cholesterol; X-Ray Crystallography; inhibitor; Isoform

Source:

Purdue University / 2024

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Co-authors:

Hillary English