Crystal structure of undecaprenyl-pyrophosphate
phosphatase and its role in peptidoglycan
Meriem El Ghachi
, Nicole Howe
, Chia-Ying Huang
, Vincent Olieric
, Rangana Warshamanage
, Dietmar Weichert
, Phillip J. Stansfeld
, Meitian Wang
, Fred Kerff
& Martin Caffrey
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.
Centre d’Ingénierie des Protéines, InBioS, Université de Liège, allée du 6 Août 19, Bât B5a, 4000 Liège, Belgium.
Membrane Structural and Functional
Biology (MS&FB) Group, School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2 D02 R590, Ireland.
Source, Paul Scherrer Institute, CH-5232 Villigen, Switzerland.
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud,
Université Paris-Saclay, 91190 Gif-sur-Yvette, Cedex, France.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
These authors contributed equally: Meriem El Ghachi, Nicole Howe. Correspondence and requests for materials should be addressed to
M.C. (email: email@example.com)