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Literature summary for 2.3.1.82 extracted from

  • Rather, P.N.; Munayyer, H.; Mann, P.A.; Hare, R.S.; Miller, G.H.; Shaw, K.J.
    Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6-N-acetyltransferase Ib and IIa proteins (1992), J. Bacteriol., 174, 3196-3203.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
isogenic plasmids pSCH4663 containing aac(6')-Ib gene and pSCHB4105 containing aac(6')-IIa gene, transferred to Escherichia coli DH5alpha Escherichia coli

Protein Variants

Protein Variants Comment Organism
L119S AAC(6')-Ib L119S. The AAC(6')-Ib protein is unable to efficiently modify gentamicin C1, 1.7% relative to sisomicin, however it is capable of modifying amikacin, 65.5% relative to sisomycin. The mutation results in a 2.8fold increase in acetylation of gentamicin C1, but causes an 8.7fold reduction in the ability to modify amikacin Escherichia coli
S119L AAC(6')-IIa S119L. The AAC(6')-IIa protein modifies gentamicin C1 at 10.1% relative to sisomicin, however it shows low activity towards amikacin, 4.1% relative to sisomycin. The mutation results in a 4.8fold reduction in the acetylation of gentamicin C1, but causes an 2fold increase in the ability to modify amikacin Escherichia coli

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Escherichia coli involved in resistance to antibiotics ?
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?

Organism

Organism UniProt Comment Textmining
Escherichia coli
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DH5alpha, AAC(6')-Ib protein and AAC(6')-IIa protein
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acetyl-CoA + 2'-N-ethylnetilmicin
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Escherichia coli CoA + N6'-acetyl-2'-N-ethylnetilmicin
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?
acetyl-CoA + amikacin the AAC(6')-Ib protein is unable to efficiently modify gentamicin C1, 1.7% relative activity to sisomicin, however it is capable of modifying amikacin, 65.5% relative activity to sisomycin. The mutant enzyme AAC(6')-Ib L119S shows a 2.8fold increase in acetylation of gentamicin C1, but a 8.7fold reduction in the ability to modify amikacin. The AAC(6')-IIa protein modifies gentamicin C1 at 10.1% relative activity to sisomicin, however it shows low activity towards amikacin, 4.1% activity relative to sisomycin. The mutation AAC(6')-IIa S119L results in a 4.8fold reduction in the acetylation of gentamicin C1, but causes an 2fold increase in the ability to modify amikacin Escherichia coli CoA + N6'-acetylamikacin
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?
acetyl-CoA + gentamicin C1 the AAC(6')-Ib protein is unable to efficiently modify gentamicin C1, 1.7% relative activity to sisomicin, however it is capable of modifying amikacin, 65.5% relative activity to sisomycin. The mutant enzyme AAC(6')-Ib L119S shows a 2.8fold increase in acetylation of gentamicin C1, but a 8.7fold reduction in the ability to modify amikacin. The AAC(6')-IIa protein modifies gentamicin C1 at 10.1% relative activity to sisomicin, however it shows low activity towards amikacin, 4.1% activity relative to sisomycin. The mutation AAC(6')-IIa S119L results in a 4.8fold reduction in the acetylation of gentamicin C1, but causes an 2fold increase in the ability to modify amikacin Escherichia coli CoA + N6'-acetylgentamicin C1
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?
acetyl-CoA + gentamicin C1a poor substrate, AAC-(6')-II type Escherichia coli CoA + N6'-acetylgentamicin C1a
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acetyl-CoA + sisomicin
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Escherichia coli CoA + N6'-acetylsisomicin
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?
acetyl-CoA + tobramycin
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Escherichia coli CoA + N6'-acetyltobramycin
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additional information a single amino acid, Leu119 in AAC(6')-Ib and S119 in AAC(6')-IIa, is largely responsible for determining the specificity of the AAC(6')-Ib and AAC(6')-IIa proteins. Changing this amino acid in either the AAC(6')-Ib or the AAC(6')-IIa protein results in a dramatic change in substrate specificity Escherichia coli ?
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additional information involved in resistance to antibiotics Escherichia coli ?
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?