3SRU

S. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolines

3SRU の概要

• エントリーDOI: 10.2210/pdb3sru/pdb
• 関連するPDBエントリー: 3SQY 3SR5 3SRQ 3SRR 3SRS 3SRW
• 分子名称: Dihydrofolate reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, N-[3'-(2,4-diaminoquinazolin-7-yl)-4'-ethoxybiphenyl-3-yl]methanesulfonamide, ... (4 entities in total)
• 機能のキーワード: dihydrofolate reductase, dhfr, drug design, enzyme inhibitors, folate, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20540.02

構造登録者

Hilgers, M. (登録日: 2011-07-07, 公開日: 2011-08-31, 最終更新日: 2024-02-28)

主引用文献

Li, X.,Hilgers, M.,Cunningham, M.,Chen, Z.,Trzoss, M.,Zhang, J.,Kohnen, L.,Lam, T.,Creighton, C.,G C, K.,Nelson, K.,Kwan, B.,Stidham, M.,Brown-Driver, V.,Shaw, K.J.,Finn, J.
Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines.
Bioorg.Med.Chem.Lett., 21:5171-5176, 2011

PubMed Abstract: Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim (TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains.

PubMed: 21831637
DOI: 10.1016/j.bmcl.2011.07.059

実験手法

X-RAY DIFFRACTION (1.7 Å)