Title: How Sulfa Drugs Work | National Institutes of Health (NIH)
Headings: How Sulfa Drugs Work
How Sulfa Drugs Work
Content: While antibiotic resistance remains a problem for this class of antibiotics, sulfa drugs are still commonly used to treat a variety of bacterial infections. Sulfa drugs work by binding and inhibiting a specific enzyme called dihydropteroate synthase (DHPS). This enzyme is critical for the synthesis of folate, an essential nutrient. Mammals get folate from their diet, but bacteria must synthesize this vitamin. Folate synthesis requires a chemical reaction between 2 molecules, DHPP and PABA, that is catalyzed by DHPS. Bacteria resistant to sulfa drugs often have mutations in the DHPS enzyme. These mutations occur on 2 floppy loops that sit near the enzyme's active site. Previous research had described most of the structure of DHPS, but the structure of the floppy, highly conserved loops remained elusive. Moreover, researchers didn't know how the chemical reaction occurs between DHPP and PABA. A team of scientists led by Dr. Stephen White of St. Jude Children's Research Hospital set out to determine the structure of the loops and the chemical reactions that are helped along by DHPS.