2YF9

STRUCTURAL AND FUNCTIONAL INSIGHTS OF DR2231 PROTEIN, THE MAZG-LIKE NUCLEOSIDE TRIPHOSPHATE PYROPHOSPHOHYDROLASE FROM DEINOCOCCUS RADIODURANS, NATIVE FORM

Summary for 2YF9

• Entry DOI: 10.2210/pdb2yf9/pdb
• Related: 2YEU 2YF3 2YF4 2YFC 2YFD
• Descriptor: MAZG-LIKE NUCLEOSIDE TRIPHOSPHATE PYROPHOSPHOHYDROLASE, CHLORIDE ION (3 entities in total)
• Functional Keywords: hydrolase, dimeric dutpase
• Biological source: DEINOCOCCUS RADIODURANS
• Total number of polymer chains: 1
• Total formula weight: 16850.50

Authors

Goncalves, A.M.D.,De Sanctis, D.,Mcsweeney, S.M. (deposition date: 2011-04-04, release date: 2011-07-06, Last modification date: 2023-12-20)

Primary citation

Goncalves, A.M.D.,Desanctis, D.,Mcsweeney, S.M.
Structural and Functional Insights Into Dr2231 Protein, the Mazg-Like Nucleoside Triphosphate Pyrophosphohydrolase from Deinococcus Radiodurans.
J.Biol.Chem., 286:30691-, 2011

PubMed Abstract: Deinococcus radiodurans is among the very few bacterial species extremely resistant to ionizing radiation, UV light, oxidizing agents, and cycles of prolonged desiccation. The proteome of D. radiodurans reflects the evolutionary pressure exerted by chronic exposure to (nonradioactive) forms of DNA and protein damage. A clear example of this adaptation is the overrepresentation of protein families involved in the removal of non-canonical nucleoside triphosphates (NTPs) whose incorporation into nascent DNA would promote mutagenesis and DNA damage. The three-dimensional structure of the DR2231 protein has been solved at 1.80 Å resolution. This protein had been classified as an all-α-helical MazG-like protein. The present study confirms that it holds the basic structural module characteristic of the MazG superfamily; two helices form a rigid domain, and two helices form a mobile domain and connecting loops. Contrary to what is known of MazG proteins, DR2231 protein shows a functional affinity with dUTPases. Enzymatic and isothermal calorimetry assays have demonstrated high specificity toward dUTP but an inability to hydrolyze dTTP, a typical feature of dUTPases. Co-crystallization with the product of hydrolysis, dUMP, in the presence of magnesium or manganese cations, suggests similarities with the dUTP/dUDP hydrolysis mechanism reported for dimeric dUTPases. The genome of D. radiodurans encodes for all enzymes required for dTTP synthesis from dCMP, thus bypassing the need of a dUTPase. We postulate that DR2231 protein is not essential to D. radiodurans and rather performs "house-cleaning" functions within the framework of oxidative stress response. We further propose DR2231 protein as an evolutionary precursor of dimeric dUTPases.

PubMed: 21733847
DOI: 10.1074/JBC.M111.247999

Experimental method

X-RAY DIFFRACTION (1.899 Å)