7CSJ

Aminoglycoside 2'-N-acetyltransferase from Mycolicibacterium smegmatis-Complex with Coenzyme A and Gentamicin

7CSJ の概要

• エントリーDOI: 10.2210/pdb7csj/pdb
• 関連するPDBエントリー: 7CRM
• 分子名称: Aminoglycoside 2'-N-acetyltransferase, gentamicin C1, COENZYME A, ... (4 entities in total)
• 機能のキーワード: aminoglycoside acetyltransferase, antibiotics, gentamicin, transferase
• 由来する生物種: Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48410.34

構造登録者

Jeong, C.S.,Hwang, J.,Do, H.,Lee, J.H. (登録日: 2020-08-14, 公開日: 2021-06-23, 最終更新日: 2023-11-29)

主引用文献

Jeong, C.S.,Hwang, J.,Do, H.,Cha, S.S.,Oh, T.J.,Kim, H.J.,Park, H.H.,Lee, J.H.
Structural and biochemical analyses of an aminoglycoside 2'-N-acetyltransferase from Mycolicibacterium smegmatis.
Sci Rep, 10:21503-21503, 2020

PubMed Abstract: The expression of aminoglycoside-modifying enzymes represents a survival strategy of antibiotic-resistant bacteria. Aminoglycoside 2'-N-acetyltransferase [AAC(2')] neutralizes aminoglycoside drugs by acetylation of their 2' amino groups in an acetyl coenzyme A (CoA)-dependent manner. To understand the structural features and molecular mechanism underlying AAC(2') activity, we overexpressed, purified, and crystallized AAC(2') from Mycolicibacterium smegmatis [AAC(2')-Id] and determined the crystal structures of its apo-form and ternary complexes with CoA and four different aminoglycosides (gentamicin, sisomicin, neomycin, and paromomycin). These AAC(2')-Id structures unraveled the binding modes of different aminoglycosides, explaining the broad substrate specificity of the enzyme. Comparative structural analysis showed that the α4-helix and β8-β9 loop region undergo major conformational changes upon CoA and substrate binding. Additionally, structural comparison between the present paromomycin-bound AAC(2')-Id structure and the previously reported paromomycin-bound AAC(6')-Ib and 30S ribosome structures revealed the structural features of paromomycin that are responsible for its antibiotic activity and AAC binding. Taken together, these results provide useful information for designing AAC(2') inhibitors and for the chemical modification of aminoglycosides.

PubMed: 33299080
DOI: 10.1038/s41598-020-78699-z

実験手法

X-RAY DIFFRACTION (2.168 Å)