5FGN

Integral membrane protein lipooligosaccharide phosphoethanolamine transferase A (EptA) from Neisseria meningitidis

5FGN の概要

• エントリーDOI: 10.2210/pdb5fgn/pdb
• 関連するPDBエントリー: 4KAV 4KAY
• 分子名称: lipooligosaccharide phosphoethanolamine transferase A, 2-O-octyl-beta-D-glucopyranose, DODECYL-BETA-D-MALTOSIDE, ... (5 entities in total)
• 機能のキーワード: endotoxin biosynthesis, epta, membrane protein, phosphoethanolamine transferase, polymixin resistance, hydrolase, phosphotransferase, transferase
• 由来する生物種: Neisseria meningitidis serogroup B
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 63160.66

構造登録者

Anandan, A.,Vrielink, A. (登録日: 2015-12-21, 公開日: 2017-02-15, 最終更新日: 2024-11-06)

主引用文献

Anandan, A.,Evans, G.L.,Condic-Jurkic, K.,O'Mara, M.L.,John, C.M.,Phillips, N.J.,Jarvis, G.A.,Wills, S.S.,Stubbs, K.A.,Moraes, I.,Kahler, C.M.,Vrielink, A.
Structure of a lipid A phosphoethanolamine transferase suggests how conformational changes govern substrate binding.
Proc. Natl. Acad. Sci. U.S.A., 114:2218-2223, 2017

PubMed Abstract: Multidrug-resistant (MDR) gram-negative bacteria have increased the prevalence of fatal sepsis in modern times. Colistin is a cationic antimicrobial peptide (CAMP) antibiotic that permeabilizes the bacterial outer membrane (OM) and has been used to treat these infections. The OM outer leaflet is comprised of endotoxin containing lipid A, which can be modified to increase resistance to CAMPs and prevent clearance by the innate immune response. One type of lipid A modification involves the addition of phosphoethanolamine to the 1 and 4' headgroup positions by phosphoethanolamine transferases. Previous structural work on a truncated form of this enzyme suggested that the full-length protein was required for correct lipid substrate binding and catalysis. We now report the crystal structure of a full-length lipid A phosphoethanolamine transferase from , determined to 2.75-Å resolution. The structure reveals a previously uncharacterized helical membrane domain and a periplasmic facing soluble domain. The domains are linked by a helix that runs along the membrane surface interacting with the phospholipid head groups. Two helices located in a periplasmic loop between two transmembrane helices contain conserved charged residues and are implicated in substrate binding. Intrinsic fluorescence, limited proteolysis, and molecular dynamics studies suggest the protein may sample different conformational states to enable the binding of two very different- sized lipid substrates. These results provide insights into the mechanism of endotoxin modification and will aid a structure-guided rational drug design approach to treating multidrug-resistant bacterial infections.

PubMed: 28193899
DOI: 10.1073/pnas.1612927114

実験手法

X-RAY DIFFRACTION (2.75 Å)