6ET8

Crystal structure of AlbA in complex with albicidin

6ET8 の概要

• エントリーDOI: 10.2210/pdb6et8/pdb
• 分子名称: Albicidin resistance protein, albicidin, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: albicidin, alba, protein binding
• 由来する生物種: Klebsiella oxytoca
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54943.89

構造登録者

Driller, R.,Rostock, L.,Alings, C.,Graetz, S.,Suessmuth, R.,Mainz, A.,Wahl, M.C.,Loll, B. (登録日: 2017-10-25, 公開日: 2018-08-15, 最終更新日: 2024-10-23)

主引用文献

Rostock, L.,Driller, R.,Gratz, S.,Kerwat, D.,von Eckardstein, L.,Petras, D.,Kunert, M.,Alings, C.,Schmitt, F.J.,Friedrich, T.,Wahl, M.C.,Loll, B.,Mainz, A.,Sussmuth, R.D.
Molecular insights into antibiotic resistance - how a binding protein traps albicidin.
Nat Commun, 9:3095-3095, 2018

PubMed Abstract: The worldwide emergence of antibiotic resistance poses a serious threat to human health. A molecular understanding of resistance strategies employed by bacteria is obligatory to generate less-susceptible antibiotics. Albicidin is a highly potent antibacterial compound synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. The drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca. Here we show that AlbA binds albicidin with low nanomolar affinity resulting in full inhibition of its antibacterial activity. We report on the crystal structure of the drug-binding domain of AlbA (AlbAS) in complex with albicidin. Both α-helical repeat domains of AlbAS are required to cooperatively clamp albicidin, which is unusual for drug-binding proteins of the MerR family. Structure-guided NMR binding studies employing synthetic albicidin derivatives give valuable information about ligand promiscuity of AlbAS. Our findings thus expand the general understanding of antibiotic resistance mechanisms and support current drug-design efforts directed at more effective albicidin analogs.

PubMed: 30082794
DOI: 10.1038/s41467-018-05551-4

実験手法

X-RAY DIFFRACTION (1.7 Å)