Aminoglycosides are one of the oldest classes of antibiotics, first discovered in 1944. Despite their long history as potent antibacterials, unfortunately they do not meet their full potential as clinical drugs, largely due to antibiotic resistance. Aminoglycoside resistance enzymes include aminoglycoside acetyltransferases (AAC) and aminoglycoside phosphotransferases or kinases (APH). The APH enzymes belong to the eukaryotic-type protein kinase (PK) superfamily. This group also contains serine/threonine and tyrosine PKs and small-molecule kinases like choline kinase. Outside of the nucleoside-binding and catalytic site, APH enzymes deviate considerably in architecture from PKs, most notably by a large expansion of the C-terminal lobe. This expansion divides the C lobe into the "core subdomain" shared with PKs that contains all of the catalytic elements, and the APH-specific "helical subdomain" PMID:27161980.

This entry represents the C-terminal lobe of APH enzymes. This domain is composed of two central 4-helical bundles, a short beta hairpin and a small two-stranded beta sheet PMID:25619172.