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Structural and biochemical analyses of an aminoglycoside 2 '-N-acetyltransferase from Mycolicibacterium smegmatis
- Title
- Structural and biochemical analyses of an aminoglycoside 2 '-N-acetyltransferase from Mycolicibacterium smegmatis
- Authors
- Jeong, Chang-Sook; Hwang, Jisub; Do, Hackwon; Cha, Sun-Shin; Oh, Tae-Jin; Kim, Hak Jun; Park, Hyun Ho; Lee, Jun Hyuck
- Ewha Authors
- 차선신
- SCOPUS Author ID
- 차선신
- Issue Date
- 2020
- Journal Title
- SCIENTIFIC REPORTS
- ISSN
- 2045-2322
- Citation
- SCIENTIFIC REPORTS vol. 10, no. 1
- Publisher
- NATURE RESEARCH
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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 alpha 4-helix and beta 8-beta 9 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.
- DOI
- 10.1038/s41598-020-78699-z
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
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