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.