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

Structure. 2018 Feb 6;26(2):295-303.e6. doi: 10.1016/j.str.2018.01.004.

Megan Carter ¹, Ann-Sofie Jemth ², Jordi Carreras-Puigvert ², Patrick Herr ², Markel Martínez Carranza ¹, Karl S A Vallin ², Adam Throup ², Thomas Helleday ³, Pål Stenmark ⁴

Affiliations

1 Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
2 Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 21 Stockholm, Sweden.
3 Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 21 Stockholm, Sweden. Electronic address: [email protected].
4 Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden. Electronic address: [email protected].

PMID: 29413322 DOI: 10.1016/j.str.2018.01.004

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.

Keywords

NUDIX; NUDT22; UDP-galactose; UDP-glucose; hydrolase.

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