3v5o

Structural and Mechanistic Studies of Catalysis and Sulfa Drug Resistance in Dihydropteroate Synthase

spinqualitylabelsall models 3v5o, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3v5o is a 2 chain structure with sequence from Bacaa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Related: 1tws Gene: folP, BAA_0084 (BACAA) Activity: Dihydropteroate synthase, with EC number 2.5.1.15 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [C3P9L8_BACAA] DHPS catalyzes the formation of the immediate precursor of folic acid.[RuleBase:RU361205] Publication Abstract from PubMed The sulfonamide antibiotics inhibit dihydropteroate synthase (DHPS), a key enzyme in the folate pathway of bacteria and primitive eukaryotes. However, resistance mutations have severely compromised the usefulness of these drugs. We report structural, computational, and mutagenesis studies on the catalytic and resistance mechanisms of DHPS. By performing the enzyme-catalyzed reaction in crystalline DHPS, we have structurally characterized key intermediates along the reaction pathway. Results support an S(N)1 reaction mechanism via formation of a novel cationic pterin intermediate. We also show that two conserved loops generate a substructure during catalysis that creates a specific binding pocket for p-aminobenzoic acid, one of the two DHPS substrates. This substructure, together with the pterin-binding pocket, explains the roles of the conserved active-site residues and reveals how sulfonamide resistance arises. Catalysis and sulfa drug resistance in dihydropteroate synthase.,Yun MK, Wu Y, Li Z, Zhao Y, Waddell MB, Ferreira AM, Lee RE, Bashford D, White SW Science. 2012 Mar 2;335(6072):1110-4. PMID:22383850 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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