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

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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)295-303.e6
JournalStructure
Volume26
Issue number2
DOIs
Publication statusPublished - 2018 Feb 6
Externally publishedYes

Bibliographical note

Copyright © 2018 Elsevier Ltd. All rights reserved.

Free keywords

  • Galactosephosphates/metabolism
  • Glucosephosphates/metabolism
  • Humans
  • Phosphoric Diester Hydrolases/metabolism
  • Protein Folding

Fingerprint

Dive into the research topics of 'Human NUDT22 Is a UDP-Glucose/Galactose Hydrolase Exhibiting a Unique Structural Fold'. Together they form a unique fingerprint.

Cite this