1TWS

Dihydropteroate Synthetase From Bacillus anthracis

1TWS の概要

• エントリーDOI: 10.2210/pdb1tws/pdb
• 関連するPDBエントリー: 1TWW 1TWZ 1TX0 1TX2
• 分子名称: DHPS, Dihydropteroate synthase, SULFATE ION (3 entities in total)
• 機能のキーワード: anthracis, folate biosynthesis, dihydropteroate, pterine, transferase
• 由来する生物種: Bacillus anthracis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66920.22

構造登録者

Babaoglu, K.,Qi, J.,Lee, R.E.,White, S.W. (登録日: 2004-07-01, 公開日: 2004-09-14, 最終更新日: 2023-08-23)

主引用文献

Babaoglu, K.,Qi, J.,Lee, R.E.,White, S.W.
Crystal Structure of 7,8-Dihydropteroate Synthase from Bacillus anthracis; Mechanism and Novel Inhibitor Design.
STRUCTURE, 12:1705-1717, 2004

PubMed Abstract: Dihydropterate synthase (DHPS) is the target for the sulfonamide class of antibiotics, but increasing resistance has encouraged the development of new therapeutic agents against this enzyme. One approach is to identify molecules that occupy the pterin binding pocket which is distinct from the pABA binding pocket that binds sulfonamides. Toward this goal, we present five crystal structures of DHPS from Bacillus anthracis, a well-documented bioterrorism agent. Three DHPS structures are already known, but our B. anthracis structures provide new insights into the enzyme mechanism. We show how an arginine side chain mimics the pterin ring in binding within the pterin binding pocket. The structures of two substrate analog complexes and the first structure of a DHPS-product complex offer new insights into the catalytic mechanism and the architecture of the pABA binding pocket. Finally, as an initial step in the development of pterin-based inhibitors, we present the structure of DHPS complexed with 5-nitro-6-methylamino-isocytosine.

PubMed: 15341734
DOI: 10.1016/j.str.2004.07.011

実験手法

X-RAY DIFFRACTION (2 Å)