7UUK
Crystal structure of aminoglycoside resistance enzyme ApmA, complex with tobramycin
Summary for 7UUK
| Entry DOI | 10.2210/pdb7uuk/pdb |
| Related | 7UUJ 7UUL 7UUM 7UUN 7UUO |
| Descriptor | Aminocyclitol acetyltransferase ApmA, TOBRAMYCIN, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | 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, center for structural biology of infectious diseases, csbid |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 3 |
| Total formula weight | 95481.86 |
| Authors | Stogios, P.J.,Evdokimova, E.,Di Leo, R.,Bordeleau, E.,Wright, G.D.,Savchenko, A.,Joachimiak, A.,Satchell, K.J.F.,Center for Structural Biology of Infectious Diseases (CSBID) (deposition date: 2022-04-28, release date: 2023-04-19, Last modification date: 2024-02-14) |
| Primary citation | 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 Cited by 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: 37973888DOI: 10.1038/s41589-023-01483-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.82 Å) |
Structure validation
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