5IGI

Macrolide 2'-phosphotransferase type I - complex with guanosine and azithromycin

5IGI の概要

• エントリーDOI: 10.2210/pdb5igi/pdb
• 関連するPDBエントリー: 5IGH 5IGJ 5IGP 5IGR 5IGS 5IGT
• 分子名称: Macrolide 2'-phosphotransferase, GUANOSINE, AZITHROMYCIN, ... (5 entities in total)
• 機能のキーワード: macrolide phosphotransferase, kinase, transferase-antibiotic complex, transferase/antibiotic
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34359.15

構造登録者

Berghuis, A.M.,Fong, D.H. (登録日: 2016-02-28, 公開日: 2017-04-26, 最終更新日: 2023-09-27)

主引用文献

Fong, D.H.,Burk, D.L.,Blanchet, J.,Yan, A.Y.,Berghuis, A.M.
Structural Basis for Kinase-Mediated Macrolide Antibiotic Resistance.
Structure, 25:750-761.e5, 2017

PubMed Abstract: The macrolides are a class of antibiotic, characterized by a large macrocyclic lactone ring that can be inactivated by macrolide phosphotransferase enzymes. We present structures for MPH(2')-I and MPH(2')-II in the apo state, and in complex with GTP analogs and six different macrolides. These represent the first structures from the two main classes of macrolide phosphotransferases. The structures show that the enzymes are related to the aminoglycoside phosphotransferases, but are distinguished from them by the presence of a large interdomain linker that contributes to an expanded antibiotic binding pocket. This pocket is largely hydrophobic, with a negatively charged patch located at a conserved aspartate residue, rationalizing the broad-spectrum resistance conferred by the enzymes. Complementary mutation studies provide insights into factors governing substrate specificity. A comparison with macrolides bound to their natural target, the 50S ribosome, suggests avenues for next-generation antibiotic development.

PubMed: 28416110
DOI: 10.1016/j.str.2017.03.007

実験手法

X-RAY DIFFRACTION (1.2 Å)