Aminoglycoside nucleotidyltransferase (4')

UniProtKB accession:  P05057

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UniProtKB description:  Inactivates aminoglycoside antibiotics such as kanamycin by catalyzing the transfer of a nucleotidyl group from a wide variety of nucleoside triphosphates ((d)ATP, (d)CTP, (d)GTP, ITP, TTP and (d)UTP) to the 4'-hydroxyl group of the aminoglycoside (PubMed:6090428, PubMed:21040710). In vitro, antibiotics without the 4'-hydroxyl but possessing a 4''-hydroxyl group (e.g. sisomicin and gentamicin) are also modifed but with poor specificity (PubMed:21040710). The 3' position of the NTP ribose ring does not tolerate large substitutions (e.g. ddATP) and dNTPs and TTP are better substrates than their NTP counterparts (PubMed:21040710). A short (2.35 Angstrom) hydrogen bond initially facilitates tight binding of the substrate (between Glu-52 and antibiotic) that is subsequently disrupted by the assembly of the active ternary complex. This enables the release of products post-catalysis, a 'catch and release' mechanism (PubMed:38250052).