7UUL

Crystal structure of aminoglycoside resistance enzyme ApmA, complex with kanamycin B and coenzyme A

7UUL の概要

• エントリーDOI: 10.2210/pdb7uul/pdb
• 関連するPDBエントリー: 7UUJ 7UUK 7UUM 7UUN 7UUO
• 分子名称: Aminocyclitol acetyltransferase ApmA, (1R,2S,3S,4R,6S)-4,6-DIAMINO-3-[(3-AMINO-3-DEOXY-ALPHA-D-GLUCOPYRANOSYL)OXY]-2-HYDROXYCYCLOHEXYL 2,6-DIAMINO-2,6-DIDEOXY-ALPHA-D-GLUCOPYRANOSIDE, COENZYME A, ... (7 entities in total)
• 機能のキーワード: xat, xenobiotic acetyltransferase, left-handed beta helix, lbh, antibiotic resistance, aminoglycoside, structural genomics, csgid, center for structural genomics of infectious diseases, niaid, national institute of allergy and infectious diseases, transferase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 196205.37

構造登録者

Stogios, P.J.,Evdokimova, E.,Di Leo, R.,Bordeleau, E.,Wright, G.D.,Savchenko, A.,Joachimiak, A.,Satchell, K.J.F.,Center for Structural Genomics of Infectious Diseases (CSGID),Center for Structural Biology of Infectious Diseases (CSBID) (登録日: 2022-04-28, 公開日: 2022-11-02, 最終更新日: 2024-02-14)

主引用文献

Bordeleau, E.,Stogios, P.J.,Evdokimova, E.,Koteva, K.,Savchenko, A.,Wright, G.D.
Mechanistic plasticity in ApmA enables aminoglycoside promiscuity for resistance.
Nat.Chem.Biol., 20:234-242, 2024

PubMed Abstract: The efficacy of aminoglycoside antibiotics is waning due to the acquisition of diverse resistance mechanisms by bacteria. Among the most prevalent are aminoglycoside acetyltransferases (AACs) that inactivate the antibiotics through acetyl coenzyme A-mediated modification. Most AACs are members of the GCN5 superfamily of acyltransferases which lack conserved active site residues that participate in catalysis. ApmA is the first reported AAC belonging to the left-handed β-helix superfamily. These enzymes are characterized by an essential active site histidine that acts as an active site base. Here we show that ApmA confers broad-spectrum aminoglycoside resistance with a molecular mechanism that diverges from other detoxifying left-handed β-helix superfamily enzymes and canonical GCN5 AACs. We find that the active site histidine plays different functions depending on the acetyl-accepting aminoglycoside substrate. This flexibility in the mechanism of a single enzyme underscores the plasticity of antibiotic resistance elements to co-opt protein catalysts in the evolution of drug detoxification.

PubMed: 37973888
DOI: 10.1038/s41589-023-01483-3

実験手法

X-RAY DIFFRACTION (2.26 Å)