9ASC

Cryo-EM Structure of the Glycosyltransferase ArnC from Salmonella enterica in the UDP-bound State Determined on Talos Arctica microscope

9ASC の概要

• エントリーDOI: 10.2210/pdb9asc/pdb
• 関連するPDBエントリー: 8VXH
• EMDBエントリー: 43812
• 分子名称: Undecaprenyl-phosphate 4-deoxy-4-formamido-L-arabinose transferase, URIDINE-5'-DIPHOSPHATE, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: glycosyltransferase, undecaprenyl phosphate, aminoarabinose, polymyxin resistance, gt-a, transferase
• 由来する生物種: Salmonella enterica subsp. enterica serovar Typhimurium str. LT2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 164738.55

構造登録者

Ashraf, K.U.,Punetha, A.,Petrou, V.I. (登録日: 2024-02-24, 公開日: 2025-02-05, 最終更新日: 2025-03-05)

主引用文献

Ashraf, K.U.,Bunoro-Batista, M.,Ansell, T.B.,Punetha, A.,Rosario-Garrido, S.,Firlar, E.,Kaelber, J.T.,Stansfeld, P.J.,Petrou, V.I.
Structural basis of undecaprenyl phosphate glycosylation leading to polymyxin resistance in Gram-negative bacteria.
Biorxiv, 2025

PubMed 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 in 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 metal-dependent polyprenyl phosphate glycosyltransferases. The reported structures provide a new target for drug design aiming to combat polymyxin resistance.

PubMed: 39974898
DOI: 10.1101/2025.01.29.634835

実験手法

ELECTRON MICROSCOPY (2.96 Å)