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

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El Ghachi, Meriem, Howe, Nicole, Huang, Chia-Ying, Olieric, Vincent, Warshamanage, Rangana, Touzé, Thierry, Weichert, Dietmar, Stansfeld, Phillip J., Wang, Meitian, Kerff, Fred and Caffrey, Martin (2018) Crystal structure of undecaprenyl-pyrophosphate phosphatase and its role in peptidoglycan biosynthesis. Nature Communications, 9 (1). 1078 . doi:10.1038/s41467-018-03477-5

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Official URL: http://dx.doi.org/10.1038/s41467-018-03477-5

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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.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Q Science > QP Physiology
Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Peptidoglycans, Pyrophosphates, Phosphatases, Biosynthesis, Crystals -- Structure
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group
ISSN: 2041-1723
Official Date: 14 March 2018
Dates:
DateEvent
14 March 2018Published
14 February 2018Accepted
Volume: 9
Number: 1
Article Number: 1078
DOI: 10.1038/s41467-018-03477-5
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
12/IA/1255Science Foundation Irelandhttp://dx.doi.org/10.13039/501100001602
P7/44Belgian Federal Science Policy Officehttp://dx.doi.org/10.13039/501100002749
MIS F.4518.12Fonds De La Recherche Scientifique - FNRShttp://dx.doi.org/10.13039/501100002661
IISN 4.4503.11Fonds De La Recherche Scientifique - FNRShttp://dx.doi.org/10.13039/501100002661
ANR-11-BSV3-002[ANR] Agence Nationale de la Recherchehttp://dx.doi.org/10.13039/501100001665
UNSPECIFIEDCentre National de la Recherche Scientifiquehttp://dx.doi.org/10.13039/501100004794
UMR 9198Université Paris-Sudhttp://dx.doi.org/10.13039/501100007486
UNSPECIFIED[DFG] Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659
UNSPECIFIEDWellcome Trusthttp://dx.doi.org/10.13039/100010269
BB/I019855/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/P01948X/1 [BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/R002517/1 [BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
R.CFRA.1567Tournesol Hubert Curien PartnershipUNSPECIFIED

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