Structural highlights
FunctionPublication Abstract from PubMedApramycin biosynthesis features an unusual O-5 phosphorylation on octose-containing pseudotrisaccharide intermediates that functions as a pathway recognition tag. AprI catalyzes 7'-N-methylation of the phosphorylated intermediate. Unexpectedly, sequence and phylogenetic analysis place AprI within the HemK/PrmC superfamily of protein-targeting methyltransferases rather than among canonical small-molecule N-methyltransferases. Here, we report the crystal structures of AprI in apo and SAH-bound forms, revealing a clasp-like homodimer formed by the N-terminal region and a highly dynamic substrate-proximal loop. Structure-guided docking, molecular dynamics simulations, and mutational analysis show that the homodimer forms a composite, positively charged pocket for recognition of the O-5 phosphate tag, whereas the flexible loop positions the 7'-amino group of the pseudotrisaccharide substrate for methyl transfer. Together, these findings establish AprI as an unusual PrmC-like protein methyltransferase repurposed for tailoring phosphorylated natural products, and open opportunities to engineer biocatalysts for site-selective aminoglycoside diversification. Phosphate-tagged substrate recognition by a PrmC-like methyltransferase in apramycin biosynthesis.,Zhang Q, Zhang Y, Cui Y, Deng Z, Zhao Q, Long F, Yu Y Int J Biol Macromol. 2026 Aug;372:153063. doi: 10.1016/j.ijbiomac.2026.153063. , Epub 2026 Jun 16. PMID:42297172[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
This page was last modified 07:06, 5 August 2026.