3SH2

Staphylococcus aureus Dihydrofolate Reductase complexed with NADPH and 6-ethyl-5-(3-(4-methoxybiphenyl-3-yl)prop-1-ynyl)pyrimidine-2,4-diamine (UCP120J)

3SH2 の概要

• エントリーDOI: 10.2210/pdb3sh2/pdb
• 関連するPDBエントリー: 3F0B 3F0Q 3F0S 3SGY
• 分子名称: Dihydrofolate reductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 6-ethyl-5-[3-(4-methoxybiphenyl-3-yl)prop-1-yn-1-yl]pyrimidine-2,4-diamine (3 entities in total)
• 機能のキーワード: oxidoreductase, nadp, nadph, one-carbon metabolism, 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: 2
• 化学式量合計: 40933.72

構造登録者

Frey, K.M.,Anderson, A.C. (登録日: 2011-06-15, 公開日: 2012-03-07, 最終更新日: 2024-04-03)

主引用文献

Viswanathan, K.,Frey, K.M.,Scocchera, E.W.,Martin, B.D.,Swain Iii, P.W.,Alverson, J.B.,Priestley, N.D.,Anderson, A.C.,Wright, D.L.
Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-Linked Antifolates Are Potent Inhibitors of MRSA and Streptococcus pyogenes.
Plos One, 7:e29434-e29434, 2012

PubMed Abstract: Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 µg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin.

PubMed: 22347365
DOI: 10.1371/journal.pone.0029434

実験手法

X-RAY DIFFRACTION (2.999 Å)