Backbone and ILVM methyl resonance assignments of human thymidylate synthase in apo and substrate bound forms.
Enzyme dynamics
NMR
Nucleotide synthesis
Thymidylate synthase
Journal
Biomolecular NMR assignments
ISSN: 1874-270X
Titre abrégé: Biomol NMR Assign
Pays: Netherlands
ID NLM: 101472371
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
11
11
2020
accepted:
08
01
2021
pubmed:
25
1
2021
medline:
17
12
2021
entrez:
24
1
2021
Statut:
ppublish
Résumé
Human thymidylate synthase (hTS) is a 72 kDa homodimeric enzyme responsible for the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), making it the sole source of de novo dTMP in human cells. As a result, hTS is an attractive anti-cancer therapeutic target. Additionally, hTS is known to possess a number of interesting biophysical features, including adoption of active and inactive conformations, positively cooperative substrate binding, half-the-sites activity, and interacting with its own mRNA. The physical mechanisms underlying these properties, and how they may be leveraged to guide therapeutic development, are yet to be fully explored. Here, as a preface to detailed NMR characterization, we present backbone amide and ILVM methyl resonance assignments for hTS in apo and dUMP bound forms. In addition, we present backbone amide resonance assignments for hTS bound to a substrate analog and the native cofactor.
Identifiants
pubmed: 33486616
doi: 10.1007/s12104-021-10006-x
pii: 10.1007/s12104-021-10006-x
pmc: PMC7979492
mid: NIHMS1666529
doi:
Substances chimiques
Thymidylate Synthase
EC 2.1.1.45
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
197-202Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008570
Pays : United States
Organisme : NCI NIH HHS
ID : P30CA016086
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : NIGMS NIH HHS
ID : 5 T32 GM 8570-22
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM083059
Pays : United States
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