4HWK
Crystal structure of human sepiapterin reductase in complex with sulfapyridine
Summary for 4HWK
| Entry DOI | 10.2210/pdb4hwk/pdb |
| Descriptor | Sepiapterin reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, SULFATE ION, ... (7 entities in total) |
| Functional Keywords | reductase, oxidoreductase-antibiotic complex, oxidoreductase/antibiotic |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P35270 |
| Total number of polymer chains | 4 |
| Total formula weight | 130852.36 |
| Authors | Groenlund Pedersen, M.,Pojer, F.,Johnsson, K. (deposition date: 2012-11-08, release date: 2013-06-05, Last modification date: 2023-09-20) |
| Primary citation | Haruki, H.,Pedersen, M.G.,Gorska, K.I.,Pojer, F.,Johnsson, K. Tetrahydrobiopterin biosynthesis as an off-target of sulfa drugs. Science, 340:987-991, 2013 Cited by PubMed Abstract: The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamethoxazole and other sulfa drugs interfere with tetrahydrobiopterin biosynthesis through inhibition of sepiapterin reductase. Crystal structures of sepiapterin reductase with bound sulfa drugs reveal how structurally diverse sulfa drugs achieve specific inhibition of the enzyme. The effect of sulfa drugs on tetrahydrobiopterin-dependent neurotransmitter biosynthesis in cell-based assays provides a rationale for some of their central nervous system-related side effects, particularly in high-dose sulfamethoxazole therapy of Pneumocystis pneumonia. Our findings reveal an unexpected aspect of the pharmacology of sulfa drugs and might translate into their improved medical use. PubMed: 23704574DOI: 10.1126/science.1232972 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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