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Crystal structure of undecaprenyl-pyrophosphate phosphatase and its role in peptidoglycan biosynthesis

DOI: 10.1038/s41467-018-03477-5 DOI Help

Authors: Meriem El Ghachi (Université de Liège) , Nicole Howe (Trinity College Dublin) , Chia-Ying Huang (Trinity College Dublin) , Vincent Olieric (Swiss Light Source) , Rangana Warshamanage (Swiss Light Source) , Thierry Touzé (Université Paris-Sud) , Dietmar Weichert (Trinity College Dublin) , Phillip J. Stansfeld (University of Oxford) , Meitian Wang (Swiss Light Source) , Fred Kerff (Université de Liège) , Martin Caffrey (Trinity College Dublin)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: March 2018
Diamond Proposal Number(s): 12710

Open Access Open Access

Abstract: As a protective envelope surrounding the bacterial cell, the peptidoglycan sacculus is a site of vulnerability and an antibiotic target. Peptidoglycan components, assembled in the cytoplasm, are shuttled across the membrane in a cycle that uses undecaprenyl-phosphate. A product of peptidoglycan synthesis, undecaprenyl-pyrophosphate, is converted to undecaprenyl-phosphate for reuse in the cycle by the membrane integral pyrophosphatase, BacA. To understand how BacA functions, we determine its crystal structure at 2.6 Å resolution. The enzyme is open to the periplasm and to the periplasmic leaflet via a pocket that extends into the membrane. Conserved residues map to the pocket where pyrophosphorolysis occurs. BacA incorporates an interdigitated inverted topology repeat, a topology type thus far only reported in transporters and channels. This unique topology raises issues regarding the ancestry of BacA, the possibility that BacA has alternate active sites on either side of the membrane and its possible function as a flippase.

Journal Keywords: Biochemistry; Structural biology; X-ray crystallography

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials

Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: X06SA-PXI at Swiss Light Source; 23-ID at Advanced Photon Source

Added On: 20/03/2018 11:12

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)