An NAD
Animals
Antibiotics, Antitubercular
/ pharmacology
Antitoxins
/ chemistry
Bacterial Load
Bacterial Proteins
/ chemistry
Bacterial Toxins
/ chemistry
Cells, Cultured
Disease Models, Animal
Female
Host-Pathogen Interactions
Humans
Kinetics
Macrophages
/ drug effects
Mice, Inbred C57BL
Mice, SCID
Mice, Transgenic
Microbial Viability
Models, Molecular
Mycobacterium smegmatis
/ enzymology
Mycobacterium tuberculosis
/ drug effects
NAD
/ metabolism
Phosphorylases
/ chemistry
Protein Conformation
Toxin-Antitoxin Systems
/ genetics
Tuberculosis
/ drug therapy
MbcTA
NAD
bacterial cell death
mycobacterium
toxin-antitoxin system
tuberculosis
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
21 03 2019
21 03 2019
Historique:
received:
26
06
2018
revised:
13
11
2018
accepted:
18
01
2019
pubmed:
23
2
2019
medline:
15
9
2020
entrez:
23
2
2019
Statut:
ppublish
Résumé
Toxin-antitoxin (TA) systems regulate fundamental cellular processes in bacteria and represent potential therapeutic targets. We report a new RES-Xre TA system in multiple human pathogens, including Mycobacterium tuberculosis. The toxin, MbcT, is bactericidal unless neutralized by its antitoxin MbcA. To investigate the mechanism, we solved the 1.8 Å-resolution crystal structure of the MbcTA complex. We found that MbcT resembles secreted NAD
Identifiants
pubmed: 30792174
pii: S1097-2765(19)30048-6
doi: 10.1016/j.molcel.2019.01.028
pmc: PMC6436930
pii:
doi:
Substances chimiques
Antibiotics, Antitubercular
0
Antitoxins
0
Bacterial Proteins
0
Bacterial Toxins
0
NAD
0U46U6E8UK
Phosphorylases
EC 2.4.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1282-1291.e8Subventions
Organisme : Cancer Research UK
ID : FC001060
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001060
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001029
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001029
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001029
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001060
Pays : United Kingdom
Informations de copyright
Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.
Références
Mol Biol Evol. 2013 Apr;30(4):772-80
pubmed: 23329690
J Bacteriol. 2014 Feb;196(4):811-24
pubmed: 24317400
Nucleic Acids Res. 2014 Apr;42(7):4590-605
pubmed: 24465005
IUCrJ. 2016 Oct 27;3(Pt 6):440-447
pubmed: 27840683
FEBS J. 2017 Sep;284(18):2932-2946
pubmed: 28383827
J Biol Chem. 2010 Feb 19;285(8):5683-94
pubmed: 20018886
Int J Med Microbiol. 2002 Feb;291(6-7):523-9
pubmed: 11890553
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2256-68
pubmed: 15572779
Nat Commun. 2017 Mar 28;8:14731
pubmed: 28348398
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
Front Microbiol. 2018 Apr 25;9:814
pubmed: 29922242
Mol Cell. 2013 Apr 11;50(1):136-48
pubmed: 23478446
Gene. 1990 Nov 30;96(1):83-8
pubmed: 2125016
Mol Cell. 2016 Dec 15;64(6):1109-1116
pubmed: 27939941
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):282-92
pubmed: 21460446
Pathog Dis. 2018 Jun 1;76(4):
pubmed: 29788125
PLoS One. 2008 Jan 30;3(1):e1502
pubmed: 18231589
Microbiol Spectr. 2014 Feb;2(1):MGM2-0018-2013
pubmed: 26082123
J Appl Crystallogr. 2015 Mar 12;48(Pt 2):431-443
pubmed: 25844078
Nucleic Acids Res. 2017 Jan 4;45(D1):D190-D199
pubmed: 27899635
Mol Microbiol. 2010 Apr;76(2):365-77
pubmed: 20199601
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):478-83
pubmed: 22505268
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Toxins (Basel). 2017 Jul 04;9(7):
pubmed: 28677629
Biochemistry. 2004 Feb 10;43(5):1204-12
pubmed: 14756556
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2184-95
pubmed: 15572771
Nat Protoc. 2012 Apr 12;7(5):872-81
pubmed: 22498707
Biophys J. 1999 Jun;76(6):2879-86
pubmed: 10354416
PLoS Pathog. 2010 Jul 08;6(7):e1000988
pubmed: 20628579
Curr Opin Microbiol. 2017 Apr;36:102-110
pubmed: 28279904
BMC Biotechnol. 2011 Mar 25;11:27
pubmed: 21439037
Cell. 2015 Oct 22;163(3):607-19
pubmed: 26456113
Mol Syst Biol. 2006;2:2006.0007
pubmed: 16738553
PLoS Pathog. 2017 Nov 27;13(11):e1006752
pubmed: 29176894
Nat Commun. 2015 Jan 22;6:6059
pubmed: 25608501
mBio. 2011 Jun 14;2(3):e00100-11
pubmed: 21673191
EMBO Rep. 2004 Feb;5(2):195-200
pubmed: 14726952
Nucleic Acids Res. 2018 Jan 4;46(D1):D493-D496
pubmed: 29040681
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):133-44
pubmed: 20124693
Nat Rev Microbiol. 2014 Sep;12(9):599-611
pubmed: 25023120
Trends Biochem Sci. 2000 Mar;25(3):147-50
pubmed: 10694887
J Struct Biol. 2011 Aug;175(2):178-88
pubmed: 21320604
IUCrJ. 2014 May 30;1(Pt 4):213-20
pubmed: 25075342
Mol Microbiol. 2019 Jan;111(1):221-236
pubmed: 30315706
PLoS Genet. 2009 Dec;5(12):e1000767
pubmed: 20011113
Nat Chem Biol. 2016 Apr;12(4):208-14
pubmed: 26991085
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Bioinformatics. 2009 May 1;25(9):1189-91
pubmed: 19151095
FEMS Microbiol Rev. 2016 Sep;40(5):592-609
pubmed: 27476076
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Toxins (Basel). 2014 Mar 06;6(3):1002-20
pubmed: 24662523
Biochem Biophys Res Commun. 1994 Nov 15;204(3):1279-85
pubmed: 7980606
mBio. 2017 Jan 17;8(1):
pubmed: 28096490
Curr Top Microbiol Immunol. 2015;384:3-32
pubmed: 25027823
Nat Struct Mol Biol. 2015 Sep;22(9):672-8
pubmed: 26237511
Sci Rep. 2017 Jul 19;7(1):5868
pubmed: 28724903
Nucleic Acids Res. 2005 Feb 01;33(2):e21
pubmed: 15687379
Infect Genet Evol. 2017 Dec;56:19-25
pubmed: 29030295
Biol Direct. 2009 Jun 03;4:19
pubmed: 19493340
J Synchrotron Radiat. 2017 Jan 1;24(Pt 1):323-332
pubmed: 28009574
Gene. 1995 Sep 22;163(1):41-6
pubmed: 7557476
Trends Microbiol. 2012 Jun;20(6):291-8
pubmed: 22445361
J Appl Crystallogr. 2009 Apr 1;42(Pt 2):342-346
pubmed: 27630371
Nat Methods. 2007 Feb;4(2):147-52
pubmed: 17179933
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):19095-100
pubmed: 24191058
Mol Cell. 2018 Jun 7;70(5):768-784
pubmed: 29398446
Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22
pubmed: 18156677
Mol Biol Evol. 2007 Aug;24(8):1861-71
pubmed: 17545187
Infect Immun. 2001 Oct;69(10):6004-11
pubmed: 11553537
Immunol Cell Biol. 2014 Sep;92(8):699-708
pubmed: 24890643
J Appl Crystallogr. 2012 Mar 15;45(Pt 2):342-350
pubmed: 25484842
Nat Struct Biol. 1999 May;6(5):458-63
pubmed: 10331874
mBio. 2014 Feb 18;5(1):
pubmed: 24549842