6CC4

Structure of MurJ from Escherichia coli

6CC4 の概要

• エントリーDOI: 10.2210/pdb6cc4/pdb
• 分子名称: soluble cytochrome b562, lipid II flippase MurJ chimera, PHOSPHATE ION (2 entities in total)
• 機能のキーワード: lipid ii flippase, mop superfamily, peptidoglycan synthesis, transport protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 66832.89

構造登録者

Zheng, S.,Kruse, A.C. (登録日: 2018-02-05, 公開日: 2018-06-27, 最終更新日: 2023-10-04)

主引用文献

Zheng, S.,Sham, L.T.,Rubino, F.A.,Brock, K.P.,Robins, W.P.,Mekalanos, J.J.,Marks, D.S.,Bernhardt, T.G.,Kruse, A.C.
Structure and mutagenic analysis of the lipid II flippase MurJ fromEscherichia coli.
Proc. Natl. Acad. Sci. U.S.A., 115:6709-6714, 2018

PubMed Abstract: The peptidoglycan cell wall provides an essential protective barrier in almost all bacteria, defining cellular morphology and conferring resistance to osmotic stress and other environmental hazards. The precursor to peptidoglycan, lipid II, is assembled on the inner leaflet of the plasma membrane. However, peptidoglycan polymerization occurs on the outer face of the plasma membrane, and lipid II must be flipped across the membrane by the MurJ protein before its use in peptidoglycan synthesis. Due to its central role in cell wall assembly, MurJ is of fundamental importance in microbial cell biology and is a prime target for novel antibiotic development. However, relatively little is known regarding the mechanisms of MurJ function, and structural data for MurJ are available only from the extremophile Here, we report the crystal structure of substrate-free MurJ from the gram-negative model organism , revealing an inward-open conformation. Taking advantage of the genetic tractability of , we performed high-throughput mutagenesis and next-generation sequencing to assess mutational tolerance at every amino acid in the protein, providing a detailed functional and structural map for the enzyme and identifying sites for inhibitor development. Lastly, through the use of sequence coevolution analysis, we identify functionally important interactions in the outward-open state of the protein, supporting a rocker-switch model for lipid II transport.

PubMed: 29891673
DOI: 10.1073/pnas.1802192115

実験手法

X-RAY DIFFRACTION (3.5 Å)