4DFU

Inhibition of an antibiotic resistance enzyme: crystal structure of aminoglycoside phosphotransferase APH(2")-ID/APH(2")-IVA in complex with kanamycin inhibited with quercetin

「3VCQ」から置き換えられました 「3R82」から置き換えられました

4DFU の概要

• エントリーDOI: 10.2210/pdb4dfu/pdb
• 関連するPDBエントリー: 4DBX 4DE4 4DFB
• 分子名称: APH(2")-Id, KANAMYCIN A, 3,5,7,3',4'-PENTAHYDROXYFLAVONE, ... (5 entities in total)
• 機能のキーワード: structural genomics, center for structural genomics of infectious diseases, csgid, eukaryotic protein kinase-like fold, transferase-antibiotic-inhibitor complex, aminoglycoside phosphotransferase, kinase, transferase, aminoglycosides, kanamycin, flavanoids, quercetin, intracellular, antibotic, transferase-antibotic-inhibitor complex, transferase/antibotic/inhibitor
• 由来する生物種: Enterococcus casseliflavus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78504.69

構造登録者

Stogios, P.J.,Minasov, G.,Dong, A.,Evdokimova, E.,Egorova, E.,Di Leo, R.,Li, H.,Shakya, T.,Wright, G.D.,Savchenko, A.,Anderson, W.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2012-01-24, 公開日: 2012-02-08, 最終更新日: 2024-11-20)

主引用文献

Shakya, T.,Stogios, P.J.,Waglechner, N.,Evdokimova, E.,Ejim, L.,Blanchard, J.E.,McArthur, A.G.,Savchenko, A.,Wright, G.D.
A small molecule discrimination map of the antibiotic resistance kinome.
Chem.Biol., 18:1591-1601, 2011

PubMed Abstract: Kinase-mediated resistance to antibiotics is a significant clinical challenge. These enzymes share a common protein fold characteristic of Ser/Thr/Tyr protein kinases. We screened 14 antibiotic resistance kinases against 80 chemically diverse protein kinase inhibitors to map resistance kinase chemical space. The screens identified molecules with both broad and narrow inhibition profiles, proving that protein kinase inhibitors offer privileged chemical matter with the potential to block antibiotic resistance. One example is the flavonol quercetin, which inhibited a number of resistance kinases in vitro and in vivo. This activity was rationalized by determination of the crystal structure of the aminoglycoside kinase APH(2″)-IVa in complex with quercetin and its antibiotic substrate kanamycin. Our data demonstrate that protein kinase inhibitors offer chemical scaffolds that can block antibiotic resistance, providing leads for co-drug design.

PubMed: 22195561
DOI: 10.1016/j.chembiol.2011.10.018

実験手法

X-RAY DIFFRACTION (1.98 Å)