3TYB

Dihydropteroate Synthase in complex with pHBA and DHP+

3TYB の概要

• エントリーDOI: 10.2210/pdb3tyb/pdb
• 関連するPDBエントリー: 1TWS
• 分子名称: Dihydropteroate synthase, 2-amino-6-methylidene-6,7-dihydropteridin-4(3H)-one, P-HYDROXYBENZOIC ACID, ... (5 entities in total)
• 機能のキーワード: anthracis, folate biosynthesis, dihydropteroate, pterine, tim barrel, transferase
• 由来する生物種: Bacillus anthracis (anthrax,anthrax bacterium)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67166.54

構造登録者

Yun, M.-K.,White, S.W. (登録日: 2011-09-24, 公開日: 2012-03-14, 最終更新日: 2023-09-13)

主引用文献

Yun, M.K.,Wu, Y.,Li, Z.,Zhao, Y.,Waddell, M.B.,Ferreira, A.M.,Lee, R.E.,Bashford, D.,White, S.W.
Catalysis and sulfa drug resistance in dihydropteroate synthase.
Science, 335:1110-1114, 2012

PubMed Abstract: 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.

PubMed: 22383850
DOI: 10.1126/science.1214641

実験手法

X-RAY DIFFRACTION (2.6 Å)