2B0Q

Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Neomycin B Complex

「1L8U」から置き換えられました

2B0Q の概要

• エントリーDOI: 10.2210/pdb2b0q/pdb
• 関連するPDBエントリー: 1J7I 1J7L 1J7U 1L8T
• 分子名称: Aminoglycoside 3'-phosphotransferase, NEOMYCIN, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: protein kinase-like, transferase
• 由来する生物種: Enterococcus faecalis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31971.31

構造登録者

Fong, D.H.,Berghuis, A.M. (登録日: 2005-09-14, 公開日: 2005-09-27, 最終更新日: 2023-08-23)

主引用文献

Fong, D.H.,Berghuis, A.M.
Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry.
Embo J., 21:2323-2331, 2002

PubMed Abstract: The misuse of antibiotics has selected for bacteria that have evolved mechanisms for evading the effects of these drugs. For aminoglycosides, a group of clinically important bactericidal antibiotics that target the A-site of the 16S ribosomal RNA, the most common mode of resistance is enzyme-catalyzed chemical modification of the drug. While aminoglycosides are structurally diverse, a single enzyme can confer resistance to many of these antibiotics. For example, the aminoglycoside kinase APH(3')-IIIa, produced by pathogenic Gram-positive bacteria such as enterococci and staphylococci, is capable of detoxifying at least 10 distinct aminoglycosides. Here we describe the crystal structures of APH(3')-IIIa in complex with ADP and kanamycin A or neomycin B. These structures reveal that the basis for this enzyme's substrate promiscuity is the presence of two alternative subsites in the antibiotic binding pocket. Furthermore, comparison between the A-site of the bacterial ribosome and APH(3')-IIIa shows that mimicry is the second major factor in dictating the substrate spectrum of APH(3')-IIIa. These results suggest a potential strategy for drug design aimed at circumventing antibiotic resistance.

PubMed: 12006485
DOI: 10.1093/emboj/21.10.2323

実験手法

X-RAY DIFFRACTION (2.7 Å)