Crystallographic analysis of TarI and TarJ, a cytidylyltransferase and reductase pair for CDP-ribitol synthesis in Staphylococcus aureus wall teichoic acid biogenesis.
Bacterial Proteins
/ chemistry
Catalytic Domain
Cell Wall
/ metabolism
Crystallography, X-Ray
Mass Spectrometry
/ methods
Models, Molecular
Mutation
Nucleoside Diphosphate Sugars
/ biosynthesis
Nucleotidyltransferases
/ chemistry
Oxidoreductases
/ chemistry
Pentosephosphates
/ metabolism
Protein Multimerization
Ribulosephosphates
/ metabolism
Staphylococcus aureus
/ cytology
Teichoic Acids
/ biosynthesis
Cell wall
Gram-positive bacteria
Peptidoglycan
Staphylococcus aureus
Teichoic acid
X-ray crystallography
Journal
Journal of structural biology
ISSN: 1095-8657
Titre abrégé: J Struct Biol
Pays: United States
ID NLM: 9011206
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
03
12
2020
revised:
29
03
2021
accepted:
30
03
2021
pubmed:
6
4
2021
medline:
27
1
2022
entrez:
5
4
2021
Statut:
ppublish
Résumé
The cell wall of many pathogenic Gram-positive bacteria contains ribitol-phosphate wall teichoic acid (WTA), a polymer that is linked to virulence and regulation of essential physiological processes including cell division. CDP-ribitol, the activated precursor for ribitol-phosphate polymerization, is synthesized by a cytidylyltransferase and reductase pair known as TarI and TarJ, respectively. In this study, we present crystal structures of Staphylococcus aureus TarI and TarJ in their apo forms and in complex with substrates and products. The TarI structures illustrate the mechanism of CDP-ribitol synthesis from CTP and ribitol-phosphate and reveal structural changes required for substrate binding and catalysis. Insights into the upstream step of ribulose-phosphate reduction to ribitol-phosphate is provided by the structures of TarJ. Furthermore, we propose a general topology of the enzymes in a heterotetrameric form built using restraints from crosslinking mass spectrometry analysis. Together, our data present molecular details of CDP-ribitol production that may aid in the design of inhibitors against WTA biosynthesis.
Identifiants
pubmed: 33819634
pii: S1047-8477(21)00038-1
doi: 10.1016/j.jsb.2021.107733
pii:
doi:
Substances chimiques
Bacterial Proteins
0
Nucleoside Diphosphate Sugars
0
Pentosephosphates
0
Ribulosephosphates
0
Teichoic Acids
0
cytidine diphosphate ribitol
3506-17-0
ribitol-5-phosphate
3506-18-1
ribulose 5-phosphate
4151-19-3
Oxidoreductases
EC 1.-
Nucleotidyltransferases
EC 2.7.7.-
D-ribitol-5-phosphate cytidylyltransferase
EC 2.7.7.40
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107733Subventions
Organisme : CIHR
Pays : Canada
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.