AAC(6')-Ib8 is an aminoglycoside 6'-N-acetyltransferase (EC 2.3.1.82) of the GNAT acetyltransferase superfamily. It transfers an acetyl group from acetyl-CoA to the 6'-amino group of 4,6-disubstituted aminoglycosides (e.g. kanamycin, amikacin, tobramycin, netilmicin), abolishing their binding to the 16S rRNA A-site and conferring aminoglycoside resistance by drug inactivation. AAC(6')-Ib is the most prevalent aminoglycoside acetyltransferase in Gram-negative clinical isolates and is typically carried as a gene cassette in class 1 integrons on plasmids; numbered allelic variants (here -Ib8) differ by point substitutions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016407 acetyltransferase activity | IEA GO_REF:0000104 | MODIFY | Summary: Correct but over-general. The specific characterised activity is aminoglycoside 6'-N-acetyltransferase activity (GO:0047663, EC 2.3.1.82), which is already annotated. Reason: Over-general parent of the specific GO:0047663 already present on this entry; the specific term should be used. Proposed replacements: aminoglycoside 6'-N-acetyltransferase activity |
| GO:0016740 transferase activity | IEA GO_REF:0000104 | MODIFY | Summary: Root-level transferase term derived from the UniProt 'Transferase' keyword; uninformative given the specific GO:0047663 annotation. Reason: Far too general (keyword-derived); subsumed by the specific aminoglycoside 6'-N-acetyltransferase activity. Proposed replacements: aminoglycoside 6'-N-acetyltransferase activity |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | MODIFY | Summary: Correct but over-general (InterPro-derived); the specific 6'-N-acetyltransferase activity is the appropriate molecular function. Reason: Over-general parent; replace with GO:0047663. Proposed replacements: aminoglycoside 6'-N-acetyltransferase activity |
| GO:0046677 response to antibiotic | IEA GO_REF:0000117 | ACCEPT | Summary: AAC(6')-Ib8 confers aminoglycoside resistance by acetylating (inactivating) the drug; 'response to antibiotic' is the appropriate biological process for a resistance enzyme. Reason: Standard, well-supported BP for an antibiotic-modifying resistance enzyme; consistent with the CARD 'antibiotic inactivation' mechanism for ARO:3002579. Supporting Evidence: PMID:18710261 Enzymatic modification of aminoglycoside antibiotics mediated by regioselective aminoglycoside N-acetyltransferases is the predominant cause of bacterial resistance to aminoglycosides. |
| GO:0047663 aminoglycoside 6'-N-acetyltransferase activity | IEA GO_REF:0000003 | ACCEPT | Summary: The specific, correct molecular function (EC 2.3.1.82): acetyl-CoA-dependent acetylation of the 6'-amino group of aminoglycosides (e.g. kanamycin B -> N(6')-acetylkanamycin B). This is the core function and exactly matches the EC and CARD AAC(6')-Ib family assignment. Reason: EC 2.3.1.82-derived specific MF, consistent with the UniProt catalytic-activity reaction (kanamycin B + acetyl-CoA = N(6')-acetylkanamycin B + CoA), the AAC(6')-Ib family (CARD ARO:3002579), and the InterPro N6_acetyl_AAC6 signature (IPR030971). Retain as the core function. Supporting Evidence: PMID:18710261 Observation of the direct, and optimally positioned, interaction between the 6'-NH |
| GO:0005737 cytoplasm | IDA PMID:18710261 Mechanistic and structural analysis of aminoglycoside N-acet... | NEW | Summary: AAC(6')-Ib is a soluble GCN5-related N-acetyltransferase (GNAT) that uses cytoplasmic acetyl-CoA; it was expressed and purified as a soluble enzyme and structurally characterized. The expected cellular location is the cytoplasm; GOA carried no location term. Reason: Soluble cytoplasmic acetyltransferase using the cytoplasmic cofactor acetyl-CoA; adding the cellular component makes the annotation set complete. Supporting Evidence: PMID:18710261 The three-dimensional structure of AAC(6')-Ib-wt was determined in various complexes with donor and acceptor ligands to resolutions greater than 2.2 |
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Download this section (compressed HTML)Q: Does AAC(6')-Ib8 carry any of the substitutions (e.g. Trp102Arg/Asp179Tyr) that, in the AAC(6')-Ib-cr variant, extend activity to fluoroquinolones, or is it a 'classical' aminoglycoside-only enzyme?
Experiment: Determine acetylation kinetics (kcat/Km) against a panel of 4,6-aminoglycosides (kanamycin, amikacin, tobramycin, netilmicin) with acetyl-CoA, and test ciprofloxacin to exclude AAC(6')-Ib-cr activity.
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