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Human NUDT22 Is a UDP-Glucose/Galactose Hydrolase Exhibiting a Unique Structural Fold.

Carter M, Jemth AS, Carreras-Puigvert J, Herr P, Martínez Carranza M, Vallin KSA, Throup A, Helleday T, Stenmark P
Structure 26 295-303.e6 (2018)
Cited: 6 times
EuropePMC logo PMID: 29413322

Abstract

Human NUDT22 belongs to the diverse NUDIX family of proteins, but has, until now, remained uncharacterized. Here we show that human NUDT22 is a Mg2+-dependent UDP-glucose and UDP-galactose hydrolase, producing UMP and glucose 1-phosphate or galactose 1-phosphate. We present the structure of human NUDT22 alone and in a complex with the substrate UDP-glucose. These structures reveal a partially conserved NUDIX fold domain preceded by a unique N-terminal domain responsible for UDP moiety binding and recognition. The NUDIX domain of NUDT22 contains a modified NUDIX box identified using structural analysis and confirmed through functional analysis of mutants. Human NUDT22's distinct structure and function as a UDP-carbohydrate hydrolase establish a unique NUDIX protein subfamily.

Reviews citing this publication (1)

  1. Nucleotide Sugars in Chemistry and Biology. Mikkola S. Molecules 25 E5755 (2020)

Articles citing this publication (5)

  1. A chronotherapeutics-applicable multi-target therapeutics based on AI: Example of therapeutic hypothermia. Liu F, Jiang X, Yang J, Tao J, Zhang M. Brief Bioinform 23 bbac365 (2022)
  2. Comparative assessment of anti-cancer drugs against NUDT15 variants to prevent leucopenia side effect in leukemia patients. V J, M S, Alsharif KF, Halawani IF, Ahmed SSSJ, Patil S. J Genet Eng Biotechnol 21 82 (2023)
  3. Development of a chemical probe against NUDT15. Zhang SM, Desroses M, Hagenkort A, Valerie NCK, Rehling D, Carter M, Wallner O, Koolmeister T, Throup A, Jemth AS, Almlöf I, Loseva O, Lundbäck T, Axelsson H, Regmi S, Sarno A, Krämer A, Pudelko L, Bräutigam L, Rasti A, Göttmann M, Wiita E, Kutzner J, Schaller T, Kalderén C, Cázares-Körner A, Page BDG, Krimpenfort R, Eshtad S, Altun M, Rudd SG, Knapp S, Scobie M, Homan EJ, Berglund UW, Stenmark P, Helleday T. Nat Chem Biol 16 1120-1128 (2020)
  4. Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy. Ottesen EW, Singh NN, Luo D, Kaas B, Gillette BJ, Seo J, Jorgensen HJ, Singh RN. Nucleic Acids Res 51 5948-5980 (2023)
  5. NUDT22 promotes cancer growth through pyrimidine salvage. Walter M, Mayr F, Hanna BMF, Cookson V, Mortusewicz O, Helleday T, Herr P. Oncogene 42 1282-1293 (2023)


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