Metabolically distinct roles of NAD synthetase and NAD kinase define the essentiality of NAD and NADP in
Mycobacterium tuberculosis
NAD
NADPH
drug targets
metabolism
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
31 08 2023
31 08 2023
Historique:
medline:
4
9
2023
pubmed:
23
6
2023
entrez:
23
6
2023
Statut:
ppublish
Résumé
Nicotinamide adenine dinucleotide (NAD) and its phosphorylated derivative (NADP) are essential cofactors that participate in hundreds of biochemical reactions and have emerged as therapeutic targets in cancer, metabolic disorders, neurodegenerative diseases, and infections, including tuberculosis. The biological basis for the essentiality of NAD(P) in most settings, however, remains experimentally unexplained. Here, we report that inactivation of the terminal enzyme of NAD synthesis, NAD synthetase (NadE), elicits markedly different metabolic and microbiologic effects than those of the terminal enzyme of NADP biosynthesis, NAD kinase (PpnK), in
Identifiants
pubmed: 37350592
doi: 10.1128/mbio.00340-23
pmc: PMC10470730
doi:
Substances chimiques
NAD+ synthase
EC 6.3.1.5
NAD
0U46U6E8UK
NAD kinase
EC 2.7.1.23
NADP
53-59-8
Ligases
EC 6.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0034023Subventions
Organisme : HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : U19AI111143
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
J Biol Chem. 2008 Jul 11;283(28):19329-41
pubmed: 18490451
Mol Microbiol. 2006 Aug;61(4):940-7
pubmed: 16879647
Mol Microbiol. 2001 Jun;40(6):1241-8
pubmed: 11442824
FEBS J. 2012 Sep;279(18):3355-63
pubmed: 22404877
PLoS Pathog. 2011 Oct;7(10):e1002287
pubmed: 21998585
J Biosci Bioeng. 2004;98(5):391-3
pubmed: 16233726
Methods Mol Biol. 2015;1285:105-15
pubmed: 25779312
Nat Struct Mol Biol. 2009 Apr;16(4):421-9
pubmed: 19270703
Chem Biol. 2010 Oct 29;17(10):1122-31
pubmed: 21035735
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6554-9
pubmed: 23576728
mBio. 2014 Feb 18;5(1):
pubmed: 24549842
Mol Microbiol. 2010 Apr;76(2):365-77
pubmed: 20199601
Biochem Biophys Res Commun. 2005 Feb 11;327(2):500-8
pubmed: 15629142
Microbiol Mol Biol Rev. 2009 Sep;73(3):529-41, Table of Contents
pubmed: 19721089
PLoS Pathog. 2014 May 22;10(5):e1004144
pubmed: 24851864
Genome Biol. 2007;8(5):R89
pubmed: 17521419
Methods Mol Biol. 2015;1285:151-75
pubmed: 25779315
Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19302-7
pubmed: 17159141
J Biosci Bioeng. 2001;92(5):447-52
pubmed: 16233126
mBio. 2017 Jan 17;8(1):
pubmed: 28096490
J Bacteriol. 2008 Jun;190(11):3886-95
pubmed: 18375549
Curr Top Microbiol Immunol. 2015;384:3-32
pubmed: 25027823
EMBO Mol Med. 2021 Jan 11;13(1):e13207
pubmed: 33283973
Sci Signal. 2009 Feb 10;2(57):mr1
pubmed: 19211509
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):19095-100
pubmed: 24191058