An antibiotic cloaked by its own resistance enzyme [15]

Journal of the American Chemical Society

Volumn 121, Issue 50, 1999, Pages 11922-11923

  Haddad, Jalal ^a   Vakulenko, Sergei ^a   Mobashery, Shahriar ^a  

^a WAYNE STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTIBIOTIC AGENT; BACTERIAL ENZYME; KANAMYCIN A; KANAMYCIN A DERIVATIVE;

CHEMICAL STRUCTURE; DRUG SYNTHESIS; ENZYME PHOSPHORYLATION; ENZYME SUBSTRATE; LETTER; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE;

EID: 0033596314     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja993452o     Document Type: Letter

References (23)

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17. Two publications (Hayashi, S. I.; Lin, E. C. C. J. Biol. Chem. 1967, 242, 1030. Rendina, A. R.; Cleland, W. W. Biochemistry 1984, 23, 5157) have shown that glycerol kinase, fructose-6-phosphate kinase, fructokinase. and hexokinase accept aldehydes and ketones as substrates. Phosphorylation of the hydrated carbonyl is followed by the release of phosphate in these cases as well.
18. Two publications (Hayashi, S. I.; Lin, E. C. C. J. Biol. Chem. 1967, 242, 1030. Rendina, A. R.; Cleland, W. W. Biochemistry 1984, 23, 5157) have shown that glycerol kinase, fructose-6-phosphate kinase, fructokinase. and hexokinase accept aldehydes and ketones as substrates. Phosphorylation of the hydrated carbonyl is followed by the release of phosphate in these cases as well.
19. -1 for APH(3′)-Ia and APH-(3′)IIa, respectively.
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21. A typical assay mixture contained 200 mM PIPES buffer (pH 7.4), 11 mM magnesium acetate, 22 mM potassium acetate, 1.8 mM PEP, 0.1 mM NADH, 6.1 units of PK, 21 units of LD, 1 μM APH(3′)-Ia, 10 μM compound 3, and 0.15 mM ATP. The final volume for each assay mixture was 1.0 mL.
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23. Antibiotics such as dibekacin and tobramycin lack the 3′-hydroxyl group and antibiotics isepamycin and amikacin have certain acyl moieties at the N-I position that make them poorer substrates for the phosphotranslerases. These molecules attempt to circumvent the resistance enzymes.