Molecule Information

General Information of the Molecule (ID: Mol00848)

• Name: Bifunctional AAC/APH (AAC/APH) ,Staphylococcus aureus
• Synonyms: AAC(6'); 2''-aminoglycoside phosphotransferase; APH(2''); R015; VRA0030
• Molecule Type: Protein
• Gene Name: aacA-aphD
• Gene ID: 58049990
• Sequence:
  MNIVENEICIRTLIDDDFPLMLKWLTDERVLEFYGGRDKKYTLESLKKHYTEPWEDEVFR
  VIIEYNNVPIGYGQIYKMYDELYTDYHYPKTDEIVYGMDQFIGEPNYWSKGIGTRYIKLI
  FEFLKKERNANAVILDPHKNNPRAIRAYQKSGFRIIEDLPEHELHEGKKEDCYLMEYRYD
  DNATNVKAMKYLIEHYFDNFKVDSIEIIGSGYDSVAYLVNNEYIFKTKFSTNKKKGYAKE
  KAIYNFLNTNLETNVKIPNIEYSYISDELSILGYKEIKGTFLTPEIYSTMSEEEQNLLKR
  DIASFLRQMHGLDYTDISECTIDNKQNVLEEYILLRETIYNDLTDIEKDYIESFMERLNA
  TTVFEGKKCLCHNDFSCNHLLLDGNNRLTGIIDFGDSGIIDEYCDFIYLLEDSEEEIGTN
  FGEDILRMYGNIDIEKAKEYQDIVEEYYPIETIVYGIKNIKQEFIENGRKEIYKRTYKD
• 3D-structure: PDB ID: 5BYL; Classification: Transferase; Method: X-ray diffraction; Resolution: 2.15 Å
• Function: Involved in resistance to gentamicin, tobramycin, and kanamycin. Tobramycin and kanamycin resistance is due to the ACC activity, specified by N-terminal region. The C-terminal region is a kinase that phosphorylates several 4,6-disubstituted aminoglycosides.
• Uniprot ID: AACA_STAAU

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Staphylococcaceae
Genus: Staphylococcus
Species: Staphylococcus aureus

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Plazomicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Bacterial infection [ICD-11: 1A00-1C4Z] [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Plazomicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Staphylococcus aureus isolates; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: AAC(6')-APH(2") is an enzyme with 6'-N-acetyltransferase and 2"-O-phosphotransferase activities.The bifunctional AAC(6')-APH(2") has the capacity to inactivate virtually all clinically important aminoglycosides through N- and O-acetylation and phosphorylation of hydroxyl groups.

References

• Ref 1: Prodigious substrate specificity of AAC(6')-APH(2"), an aminoglycoside antibiotic resistance determinant in enterococci and staphylococci. Chem Biol. 1999 Feb;6(2):99-110. doi: 10.1016/S1074-5521(99)80006-4.
• Ref 2: The aacA-aphD gentamicin and kanamycin resistance determinant of Tn4001 from Staphylococcus aureus: expression and nucleotide sequence analysis. J Gen Microbiol. 1987 Nov;133(11):3039-52. doi: 10.1099/00221287-133-11-3039.