The Heptaprenyl Diphosphate Synthase (Coq1) Is the Target of a Lipophilic Bisphosphonate That Protects Mice against Toxoplasma gondii Infection.
Toxoplasma gondii
bisphosphonate
isoprenoids
mitochondria
ubiquinone
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
26 10 2022
26 10 2022
Historique:
pubmed:
22
9
2022
medline:
29
10
2022
entrez:
21
9
2022
Statut:
ppublish
Résumé
Prenyldiphosphate synthases catalyze the reaction of allylic diphosphates with one or more isopentenyl diphosphate molecules to form compounds such as farnesyl diphosphate, used in, e.g., sterol biosynthesis and protein prenylation, as well as longer "polyprenyl" diphosphates, used in ubiquinone and menaquinone biosynthesis. Quinones play an essential role in electron transport and are associated with the inner mitochondrial membrane due to the presence of the polyprenyl group. In this work, we investigated the synthesis of the polyprenyl diphosphate that alkylates the ubiquinone ring precursor in Toxoplasma gondii, an opportunistic pathogen that causes serious disease in immunocompromised patients and the unborn fetus. The enzyme that catalyzes this early step of the ubiquinone synthesis is Coq1 (TgCoq1), and we show that it produces the C35 species heptaprenyl diphosphate. TgCoq1 localizes to the mitochondrion and is essential for
Identifiants
pubmed: 36129297
doi: 10.1128/mbio.01966-22
pmc: PMC9600589
doi:
Substances chimiques
Diphosphates
0
Diphosphonates
0
Sterols
0
trans-hexaprenyltranstransferase
EC 2.5.1.30
Ubiquinone
1339-63-5
Ubiquinone Q1
JR17826E4G
Vitamin K 2
11032-49-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0196622Subventions
Organisme : NIAID NIH HHS
ID : R01 AI169846
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI147661
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI060546
Pays : United States
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