Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Bacteriophage T5 dUTPase: Combination of Common Enzymatic and a Novel Function

Version 1 : Received: 14 December 2023 / Approved: 15 December 2023 / Online: 15 December 2023 (12:13:04 CET)

A peer-reviewed article of this Preprint also exists.

Glukhov, A.; Marchenkov, V.; Dzhus, U.; Krutilina, A.; Selikhanov, G.; Gabdulkhakov, A. Bacteriophage T5 dUTPase: Combination of Common Enzymatic and Novel Functions. Int. J. Mol. Sci. 2024, 25, 892. Glukhov, A.; Marchenkov, V.; Dzhus, U.; Krutilina, A.; Selikhanov, G.; Gabdulkhakov, A. Bacteriophage T5 dUTPase: Combination of Common Enzymatic and Novel Functions. Int. J. Mol. Sci. 2024, 25, 892.

Abstract

The main function of dUTPases is to regulate the cellular levels of dUTP and dTTP, thereby playing a crucial role in the DNA repair mechanisms. Despite the fact that mutant organisms with the obliterated dUTPase enzymatic activity remain viable, it is not possible to knockout the dut gene completely due to the lethal consequences of such mutation for the organism. As a result, it is considered that this class of enzymes perform an additional function that is essential for the organism's survival. In this study, we provide the evidence that the dUTPase of bacteriophage T5 possesses supplemental function in addition to its canonical role. We determined the crystal structure of bacteriophage T5 dUTPase with a resolution of 2.0 Å, and discovered a distinct short loop, consisting of 6 amino acid residues which represents unique structural feature specific to the T5-like phages dUTPases. The removal of this element did not affect the overall structure of the homotrimer, but had significant effects on the development of the phage. Furthermore, it has been shown that the enzymatic function and the novel function of bacteriophage T5 dUTPase are unrelated and independent from each other.

Keywords

bacteriophage; T5; dUTPase; deoxyuridine triphosphate nucleotidohydrolases; dUTP

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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