Structural Basis of Bifunctional CTP/dCTP Synthase.

Autor: Guo CJ; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Zhang Z; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH 03755, USA., Lu JL; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Zhong J; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Wu YF; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Guo SY; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Liu JL; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom. Electronic address: liujl3@shanghaitech.edu.cn.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2024 Oct 15; Vol. 436 (20), pp. 168750. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1016/j.jmb.2024.168750
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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