23LQ

Crystal structure of AprI

Summary for 23LQ

• Entry DOI: 10.2210/pdb23lq/pdb
• Descriptor: Putative oxidase > apramycin biosynthesisN-methyltransferase (2 entities in total)
• Functional Keywords: apramycin, n-methyltransferase, biosynthetic protein
• Biological source: Streptoalloteichus tenebrarius
• Total number of polymer chains: 4
• Total formula weight: 114753.65

Authors

Yu, Y.,Zhang, Q.,Zhang, Y.X. (deposition date: 2026-02-10, release date: 2026-08-05)

Primary citation

Zhang, Q.,Zhang, Y.,Cui, Y.,Deng, Z.,Zhao, Q.,Long, F.,Yu, Y.
Phosphate-tagged substrate recognition by a PrmC-like methyltransferase in apramycin biosynthesis.
Int.J.Biol.Macromol., 372:153063-153063, 2026

PubMed Abstract: Apramycin 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.

PubMed: 42297172
DOI: 10.1016/j.ijbiomac.2026.153063

Experimental method

X-RAY DIFFRACTION (2.51 Å)