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
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Molecule Type
Protein
Gene Name
aacA-aphD
Gene ID
58049990
Sequence
MNIVENEICIRTLIDDDFPLMLKWLTDERVLEFYGGRDKKYTLESLKKHYTEPWEDEVFR
VIIEYNNVPIGYGQIYKMYDELYTDYHYPKTDEIVYGMDQFIGEPNYWSKGIGTRYIKLI
FEFLKKERNANAVILDPHKNNPRAIRAYQKSGFRIIEDLPEHELHEGKKEDCYLMEYRYD
DNATNVKAMKYLIEHYFDNFKVDSIEIIGSGYDSVAYLVNNEYIFKTKFSTNKKKGYAKE
KAIYNFLNTNLETNVKIPNIEYSYISDELSILGYKEIKGTFLTPEIYSTMSEEEQNLLKR
DIASFLRQMHGLDYTDISECTIDNKQNVLEEYILLRETIYNDLTDIEKDYIESFMERLNA
TTVFEGKKCLCHNDFSCNHLLLDGNNRLTGIIDFGDSGIIDEYCDFIYLLEDSEEEIGTN
FGEDILRMYGNIDIEKAKEYQDIVEEYYPIETIVYGIKNIKQEFIENGRKEIYKRTYKD
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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.
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Uniprot ID
AACA_STAAU
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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
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Plazomicin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Disease Class: Bacterial infection [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
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.

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