6EBU

Crystal structure of Aquifex aeolicus LpxE

Summary for 6EBU

• Entry DOI: 10.2210/pdb6ebu/pdb
• Descriptor: LpxE, SULFATE ION, octyl beta-D-glucopyranoside, ... (4 entities in total)
• Functional Keywords: lpxe, lipid a 1-phosphatase, uppp, hydrolase
• Biological source: Aquifex aeolicus (strain VF5)
• Total number of polymer chains: 1
• Total formula weight: 21994.26

Authors

Wu, Q.,Wang, S.,Zhou, P. (deposition date: 2018-08-07, release date: 2019-06-26, Last modification date: 2024-03-13)

Primary citation

Zhao, J.,An, J.,Hwang, D.,Wu, Q.,Wang, S.,Gillespie, R.A.,Yang, E.G.,Guan, Z.,Zhou, P.,Chung, H.S.
The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis.
Mbio, 10:-, 2019

PubMed Abstract: Although distinct lipid phosphatases are thought to be required for processing lipid A (component of the outer leaflet of the outer membrane), glycerophospholipid (component of the inner membrane and the inner leaflet of the outer membrane), and undecaprenyl pyrophosphate (C-PP; precursors of peptidoglycan and O antigens of lipopolysaccharide) in Gram-negative bacteria, we report that the lipid A 1-phosphatases, LpxEs, functionally connect multiple layers of cell envelope biogenesis in Gram-negative bacteria. We found that LpxE structurally resembles YodM in , a phosphatase for phosphatidylglycerol phosphate (PGP) with a weak activity on C-PP, and rescues deficient in PGP and C-PP phosphatase activities; deletion of in reduces the MIC value of bacitracin, indicating a significant contribution of LpxE to the native bacterial C-PP phosphatase activity. Suppression of plasmid-borne in deficient in chromosomally encoded C-PP phosphatase activities results in cell enlargement, loss of O-antigen repeats of lipopolysaccharide, and ultimately cell death. These discoveries implicate LpxE as the first example of a multifunctional regulatory enzyme that orchestrates lipid A modification, O-antigen production, and peptidoglycan biogenesis to remodel multiple layers of the Gram-negative bacterial envelope. Dephosphorylation of the lipid A 1-phosphate by LpxE in Gram-negative bacteria plays important roles in antibiotic resistance, bacterial virulence, and modulation of the host immune system. Our results demonstrate that in addition to removing the 1-phosphate from lipid A, LpxEs also dephosphorylate undecaprenyl pyrophosphate, an important metabolite for the synthesis of the essential envelope components, peptidoglycan and O-antigen. Therefore, LpxEs participate in multiple layers of biogenesis of the Gram-negative bacterial envelope and increase antibiotic resistance. This discovery marks an important step toward understanding the regulation and biogenesis of the Gram-negative bacterial envelope.

PubMed: 31213552
DOI: 10.1128/mBio.00886-19

Experimental method

X-RAY DIFFRACTION (2.372 Å)