O ‐Carbamoyltransferase TobZ

Abstract

O ‐carbamoyltransferases, which modify a variety of natural products, exhibit an intriguing requirement for ATP. The structure of the 6″‐ O ‐carbamoyltransferase TobZ, responsible for biotransformation of the aminoglycoside antibiotic tobramycin to form nebramycin 5′, reveals two modular domains each harboring an active center within a common “reaction chamber”. The C‐terminal YrdC‐like domain harbors a carbamoylphosphate‐binding site, occupation of which triggers Mg 2+ –ATP binding and the subsequent formation of carbamoyladenylate. The adenylated intermediate is channeled to an iron‐mediated nucleotide‐binding site within the N‐terminal Kae1‐like domain, where the carbamoyl moiety is transferred to the tobramycin acceptor hydroxyl group. Conservation of modules within the hydrogenase maturation factor HypF as well as components of the ubiquitous threonylcarbamoyladenosine‐tRNA modification apparatus suggests analogous reaction sequences and points to an ancient origin of these proteins.