1AJ2

CRYSTAL STRUCTURE OF A BINARY COMPLEX OF E. COLI DIHYDROPTEROATE SYNTHASE

1AJ2 の概要

• エントリーDOI: 10.2210/pdb1aj2/pdb
• 分子名称: DIHYDROPTEROATE SYNTHASE, SULFATE ION, [7,8-DIHYDRO-PTERIN-6-YL METHANYL]-PHOSPHONOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: antibiotic, resistance, transferase, folate, biosynthesis, synthase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31103.30

構造登録者

Achari, A.,Somers, D.O.,Champness, J.N.,Bryant, P.K.,Rosemond, J.,Stammers, D.K. (登録日: 1997-05-14, 公開日: 1998-05-20, 最終更新日: 2024-02-07)

主引用文献

Achari, A.,Somers, D.O.,Champness, J.N.,Bryant, P.K.,Rosemond, J.,Stammers, D.K.
Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase.
Nat.Struct.Biol., 4:490-497, 1997

PubMed Abstract: Sulfonamides were amongst the first clinically useful antibacterial agents to be discovered. The identification of sulfanilamide as the active component of the dye Prontosil rubrum led to the synthesis of clinically useful analogues. Today sulfamethoxazole (in combination with trimethoprim), is used to treat urinary tract infections caused by bacteria such as Escherichia coli and is also a first-line treatment for pneumonia caused by the fungus Pneumocystis carinii, a common condition in AIDS patients. The site of action is the de novo folate biosynthesis enzyme dihydropteroate synthase (DHPS) where sulfonamides act as analogues of one of the substrates, para-aminobenzoic acid (pABA). We report here the crystal structure of E.coli DHPS at 2.0 A resolution refined to an R-factor of 0.185. The single domain of 282 residues forms an eight-stranded alpha/beta-barrel. The 7,8-dihydropterin pyrophosphate (DHPPP) substrate binds in a deep cleft in the barrel, whilst sulfanilamide binds closer to the surface. The DHPPP ligand site is highly conserved amongst prokaryotic and eukaryotic DHPSs.

PubMed: 9187658
DOI: 10.1038/nsb0697-490

実験手法

X-RAY DIFFRACTION (2 Å)