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.
Original language | English |
---|---|
Pages (from-to) | 295-303.e6 |
Journal | Structure |
Volume | 26 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2018 Feb 6 |
Externally published | Yes |
Bibliographical note
Copyright © 2018 Elsevier Ltd. All rights reserved.Free keywords
- Galactosephosphates/metabolism
- Glucosephosphates/metabolism
- Humans
- Phosphoric Diester Hydrolases/metabolism
- Protein Folding