3H24

Structural Studies of Pterin-Based Inhibitors of Dihydropteroate Synthase

3H24 の概要

• エントリーDOI: 10.2210/pdb3h24/pdb
• 関連するPDBエントリー: 1TWS 1TWW 1TWZ 1TX0 1TX2 3H21 3H22 3H23 3H26 3H2A 3H2C 3H2E 3H2F 3H2M 3H2N 3H2O
• 分子名称: Dihydropteroate synthase, 2-amino-8-sulfanyl-1,9-dihydro-6H-purin-6-one, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: anthracis, folate biosynthesis, dihydropteroate, pterine, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Bacillus anthracis str. A2012
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67286.61

構造登録者

Yun, M.-K.,White, S.W. (登録日: 2009-04-14, 公開日: 2009-12-08, 最終更新日: 2023-09-06)

主引用文献

Hevener, K.E.,Yun, M.K.,Qi, J.,Kerr, I.D.,Babaoglu, K.,Hurdle, J.G.,Balakrishna, K.,White, S.W.,Lee, R.E.
Structural studies of pterin-based inhibitors of dihydropteroate synthase.
J.Med.Chem., 53:166-177, 2010

PubMed Abstract: Dihydropteroate synthase (DHPS) is a key enzyme in bacterial folate synthesis and the target of the sulfonamide class of antibacterials. Resistance and toxicities associated with sulfonamides have led to a decrease in their clinical use. Compounds that bind to the pterin binding site of DHPS, as opposed to the p-amino benzoic acid (pABA) binding site targeted by the sulfonamide agents, are anticipated to bypass sulfonamide resistance. To identify such inhibitors and map the pterin binding pocket, we have performed virtual screening, synthetic, and structural studies using Bacillus anthracis DHPS. Several compounds with inhibitory activity have been identified, and crystal structures have been determined that show how the compounds engage the pterin site. The structural studies identify the key binding elements and have been used to generate a structure-activity based pharmacophore map that will facilitate the development of the next generation of DHPS inhibitors which specifically target the pterin site.

PubMed: 19899766
DOI: 10.1021/jm900861d

実験手法

X-RAY DIFFRACTION (2.5 Å)