Aminoglycoside-6-phosphotransferase

J. R. Cox and E. H. Serpersu, Biologically important conformations of aminoglycoside antibiotics bound to an aminoglycoside 3 -phosphotransferase as determined by transferred nuclear overhauser effect spectroscopy. Biochemistry, 36 (1997) 2353-2359. 

C. Oezen and E. H. Serpersu, Thermodynamics of aminoglycoside binding to aminoglycoside-3 -phosphotransferase Ilia studied by isothermal titration calorimetry, Biochemistry, 43 (2004) 14667-14675. 

Aminoglycoside-3 -phosphotransferase ) Aminoglycoside-2 -acetylase Aminoglycoside-2 -adenylase Alkyl sulphohydrolase... 

Wright GD, Thompson PR. Aminoglycoside phosphotransferases proteins, structure, and mechanism. Eront. Biosci. 1999 4 D9-D21. 

Fig. 13.5 Structure of kanamycin B showing system of ring numbering and sites of action of some aminoglycosidemodifying enzymes. AAC, aminoglycoside acetyltransferase ANT, aminoglycoside nucleotidyltransferase and APH, aminoglycoside phosphotransferase.

Ward JM, Janssen GR, Kieser T, Bibb MJ, Buttner MJ. Construction and characterisation of a series of multi-copy promoter-probe plasmid vectors for Streptomyces using the aminoglycoside phosphotransferase gene from TnS as indicator. Mol Gen Genet 1986 203 468— 478. 

Beside AAC enzymes two different enzyme classes, nucleotidyltransferases (ANT enzymes), and phosphotransferases (APH enzymes) modify the hydroxyl groups of aminocyclitol-aminoglycoside antibiotics. 

In order to analyze the effect that conformational restriction has on the antibiotic enzymatic inactivation, three different enzymes were chosen as model systems Staphylococcus aureus ANT(4 ), Mycobacterium tuberculosis AAC(2 ) and Enterococcus faecalis APH(3 ). These proteins are representative of the three main families of enzymes that modify aminoglycosides adenyltrans-ferases, acyltransferases and phosphotransferases. In addition, there is high resolution X-ray structural information available for the three enzymes in complex with several antibiotics. 

Gene encoding acid phosphatase/ phosphotransferase confers resistance to aminoglycosides... 

Structures of several important aminoglycoside antibiotics. Ring II is 2-deoxystreptamine. The resemblance between kanamycin and amikacin and between gentamicin, netilmicin, and tobramycin can be seen. The circled numerals on the kanamycin molecule indicate points of attack of plasmid-mediated bacterial transferase enzymes that can inactivate this drug. , , and , acetyltransferase , phosphotransferase , adenylyltransferase. Amikacin is resistant to modification at , , , and . 

Resistance can be caused by 1) decreased uptake of drug when the oxygen-dependent transport system for aminoglycosides is absent an altered receptor where the 30S ribosomal subunit binding site has a lowered affinity for aminoglycosides plasmid-associated synthesis of enzymes (for example, acetyltransferases, nucleotidyltransferases, and phosphotransferases) that modify and inactivate aminoglycoside... 

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