Next generation Glucose-1-phosphate thymidylyltransferase (RmlA) inhibitors: An extended SAR study to direct future design.
Antibacterial drug discovery
Bacterial cell wall synthesis
RmlA
Structure-based optimization
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 11 2021
15 11 2021
Historique:
received:
20
08
2021
revised:
07
10
2021
accepted:
11
10
2021
pubmed:
11
11
2021
medline:
14
1
2022
entrez:
10
11
2021
Statut:
ppublish
Résumé
The monosaccharide l-Rhamnose is an important component of bacterial cell walls. The first step in the l-rhamnose biosynthetic pathway is catalysed by glucose-1-phosphate thymidylyltransferase (RmlA), which condenses glucose-1-phosphate (Glu-1-P) with deoxythymidine triphosphate (dTTP) to yield dTDP-d-glucose. In addition to the active site where catalysis of this reaction occurs, RmlA has an allosteric site that is important for its function. Building on previous reports, SAR studies have explored further the allosteric site, leading to the identification of very potent P. aeruginosa RmlA inhibitors. Modification at the C6-NH
Identifiants
pubmed: 34757294
pii: S0968-0896(21)00485-5
doi: 10.1016/j.bmc.2021.116477
pmc: PMC8613358
pii:
doi:
Substances chimiques
Pyrimidinones
0
Nucleotidyltransferases
EC 2.7.7.-
glucose-1-phosphate thymidylyltransferase
EC 2.7.7.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116477Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Références
FEMS Microbiol Lett. 2007 Oct;275(2):237-43
pubmed: 17784859
Nat Rev Microbiol. 2015 Oct;13(10):605-19
pubmed: 26373371
J Biol Chem. 2001 Jun 8;276(23):19845-54
pubmed: 11279114
Metallomics. 2014 Mar;6(3):408-20
pubmed: 24481292
J Org Chem. 2013 Oct 4;78(19):9822-33
pubmed: 24020932
Tuberculosis (Edinb). 2003;83(1-3):91-7
pubmed: 12758196
Chembiochem. 2008 Sep 22;9(14):2197-9
pubmed: 18780384
Chem Biol. 1996 Dec;3(12):1011-9
pubmed: 9000006
EMBO J. 2000 Dec 15;19(24):6652-63
pubmed: 11118200
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):22-5
pubmed: 20057045
ACS Chem Biol. 2013 Feb 15;8(2):387-96
pubmed: 23138692
Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
pubmed: 15299926
Ann N Y Acad Sci. 2019 Jan;1435(1):18-38
pubmed: 29446459
J Mol Biol. 2001 Nov 2;313(4):831-43
pubmed: 11697907
J Biol Chem. 2002 Nov 15;277(46):44214-9
pubmed: 12171937
Nat Rev Drug Discov. 2013 May;12(5):371-87
pubmed: 23629505
Acta Crystallogr D Biol Crystallogr. 2000 Nov;56(Pt 11):1501-4
pubmed: 11053865
Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1355-63
pubmed: 15272157
Biometals. 2009 Aug;22(4):615-24
pubmed: 19214755
Trends Pharmacol Sci. 2014 Sep;35(9):442-9
pubmed: 25108321
Res Microbiol. 1991 May;142(4):451-63
pubmed: 1871433
Biometals. 1998 Jan;11(1):1-12
pubmed: 9450313
Bioorg Med Chem. 2010 Jan 15;18(2):896-908
pubmed: 19969466
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):386-94
pubmed: 21460457
Nature. 2017 May 18;545(7654):299-304
pubmed: 28489819
Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):48-57
pubmed: 16369093
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Nat Struct Biol. 2001 Jun;8(6):545-51
pubmed: 11373625
Adv Bioinformatics. 2016;2016:9841250
pubmed: 26981117
Nat Rev Drug Discov. 2007 Nov;6(11):881-90
pubmed: 17971784