Structural basis of undecaprenyl phosphate glycosylation leading to polymyxin resistance in Gram-negative bacteria.

ABSTRACT: In Gram-negative bacteria, the enzymatic modification of Lipid A with aminoarabinose (L-Ara4N) leads to resistance against polymyxin antibiotics and cationic antimicrobial peptides. ArnC, an integral membrane glycosyltransferase, attaches a formylated form of aminoarabinose to the lipid undecaprenyl phosphate, enabling its association with the bacterial inner membrane. Here, we present cryo-electron microscopy structures of ArnC from S. enterica in apo and nucleotide-bound conformations. These structures reveal a conformational transition that takes place upon binding of the partial donor substrate. Using coarse-grained and atomistic simulations, we provide insights into substrate coordination before and during catalysis, and we propose a catalytic mechanism that may operate on all similar

SUBMITTER: Ashraf KU 

PROVIDER: S-EPMC12690121 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature