There are five members of the
Aminoglycoside O-Nucleotidyltransferases (ANT) family of enzymes, ANT(2 ), ANT(4
ANT(2 )-Ia is a highly prevalent cause of gentamicin resistance in North America and is one of the most clinically significant members of this family of enzymes , and it is widespread among Gram-negatives. The ant(2 )-Ia gene has been found on small nonconjugative plasmids, conjugative plasmids, transposons and integrons. The enzyme follows a kinetic mechanism in which the Mg–ATP complex first binds to ANT(2 )-Ia followed by the binding of the aminoglycoside, leading to the transfer of the adenyl moiety to the aminoglycoside. The rate-limiting step of this reaction is the release of the adenylylated aminoglycoside [2-4].
The NMR structure of the isepamicin
bound to the enzyme together with a Cr–ATP complex has been reported . The
One subunit contributes the residues
required for binding ATP and Mg2+, and the other subunit provides Lys149
required for transfer the adenyl moiety to the target aminoglycoside. Both
subunits are involved in aminoglycoside binding, and the intersection of the two
1. Miller, G. H.; Sabatelli, F. J.; Naples, L.; Hare, R. S.; Shaw, K. J.; J. Chemother. 1995, 7 Suppl. 2, 17.
2. Gates, C. A.; Northrop, D. B. Biochemistry 1988, 27, 3820.
3. Gates, C. A.; Northrop, D. B. Biochemistry 1988, 27, 3826.
4. Gates, C. A.; Northrop, D. B. Biochemistry 1988, 27, 3834.
5. Ekman, D. R.; DiGiammarino, E. L.; Wright, E.; Witter, E. D.; Serpersu, E. H. Biochemistry 2001, 40, 7017.
6. Pedersen, L. C.; Benning, M. M.; Holden, H. M. Biochemsitry 1995, 34, 13305.
7. Holm, L.; Sander, C. Trends Biol. Chem. 1995, 20, 345.
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