Structural Basis of Bifunctional CTP/dCTP Synthase.
J Mol Biol
; 436(20): 168750, 2024 Oct 15.
Article
in En
| MEDLINE
| ID: mdl-39173734
ABSTRACT
The final step in the de novo synthesis of cytidine 5'-triphosphate (CTP) is catalyzed by CTP synthase (CTPS), which can form cytoophidia in all three domains of life. Recently, we have discovered that CTPS binds to ribonucleotides (NTPs) to form filaments, and have successfully resolved the structures of Drosophila melanogaster CTPS bound with NTPs. Previous biochemical studies have shown that CTPS can bind to deoxyribonucleotides (dNTPs) to produce 2'-deoxycytidine-5'-triphosphate (dCTP). However, the structural basis of CTPS binding to dNTPs is still unclear. In this study, we find that Drosophila CTPS can also form filaments with dNTPs. Using cryo-electron microscopy, we are able to resolve the structure of Drosophila melanogaster CTPS bound to dNTPs with a resolution of up to 2.7 Å. By combining these structural findings with biochemical analysis, we compare the binding and reaction characteristics of NTPs and dNTPs with CTPS. Our results indicate that the same enzyme can act bifunctionally as CTP/dCTP synthase in vitro, and provide a structural basis for these activities.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbon-Nitrogen Ligases
/
Cryoelectron Microscopy
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Drosophila melanogaster
Limits:
Animals
Language:
En
Journal:
J Mol Biol
Year:
2024
Document type:
Article
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