5JG0

Staphylococcus aureus Dihydrofolate Reductase complexed with beta-NADPH and UCP1191

5JG0 の概要

• エントリーDOI: 10.2210/pdb5jg0/pdb
• 分子名称: Dihydrofolate reductase, 4-{6-[(2S)-4-(2,4-diamino-6-ethylpyrimidin-5-yl)but-3-yn-2-yl]-2H-1,3-benzodioxol-4-yl}benzoic acid, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, dihydrofolate reductase, nadph, zwitterion, antibiotics
• 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: 19189.42

構造登録者

Anderson, A.C.,Reeve, S.M. (登録日: 2016-04-19, 公開日: 2017-04-19, 最終更新日: 2024-03-06)

主引用文献

Reeve, S.M.,Scocchera, E.W.,G-Dayanadan, N.,Keshipeddy, S.,Krucinska, J.,Hajian, B.,Ferreira, J.,Nailor, M.,Aeschlimann, J.,Wright, D.L.,Anderson, A.C.
MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates.
Cell Chem Biol, 23:1458-1467, 2016

PubMed Abstract: Antibiotic resistance is a rapidly evolving health concern that requires a sustained effort to understand mechanisms of resistance and to develop new agents that overcome those mechanisms. The dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), remains one of the most important orally administered antibiotics. However, resistance through chromosomal mutations and mobile, plasmid-encoded insensitive DHFRs threatens the continued use of this agent. We are pursuing the development of new propargyl-linked antifolate (PLA) DHFR inhibitors designed to evade these mechanisms. While analyzing contemporary TMP-resistant clinical isolates of methicillin-resistant and sensitive Staphylococcus aureus, we discovered two mobile resistance elements, dfrG and dfrK. This is the first identification of these resistance mechanisms in the United States. These resistant organisms were isolated from a variety of infection sites, show clonal diversity, and each contain distinct resistance genotypes for common antibiotics. Several PLAs showed significant activity against these resistant strains by direct inhibition of the TMP resistance elements.

PubMed: 27939900
DOI: 10.1016/j.chembiol.2016.11.007

実験手法

X-RAY DIFFRACTION (1.879 Å)