9IZ2

Focus refinement dmCTPS bound with dATP dUTP dGTP and DON

Replaces:  8I0H

Summary for 9IZ2

• Entry DOI: 10.2210/pdb9iz2/pdb
• EMDB information: 61009
• Descriptor: CTP synthase, 6-DIAZENYL-5-OXO-L-NORLEUCINE, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: ctps, filament, inhibitor, substrates, intermediate, ligase
• Biological source: Drosophila melanogaster (fruit fly)
• Total number of polymer chains: 3
• Total formula weight: 189084.87

Authors

Guo, C.J.,Liu, J.L. (deposition date: 2024-07-31, release date: 2024-11-27)

Primary citation

Guo, C.J.,Zhang, Z.,Lu, J.L.,Zhong, J.,Wu, Y.F.,Guo, S.Y.,Liu, J.L.
Structural Basis of Bifunctional CTP/dCTP Synthase.
J.Mol.Biol., 436:168750-168750, 2024

PubMed 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.

PubMed: 39173734
DOI: 10.1016/j.jmb.2024.168750

Experimental method

ELECTRON MICROSCOPY (2.79 Å)