Human NUDT22 Is a UDP-Glucose/Galactose Hydrolase Exhibiting a Unique Structural Fold
(2018) In Structure 26(2). p.6-303- 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... (More)
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.
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- author
- Carter, Megan ; Jemth, Ann-Sofie ; Carreras-Puigvert, Jordi ; Herr, Patrick ; Martínez Carranza, Markel ; Vallin, Karl S A ; Throup, Adam ; Helleday, Thomas and Stenmark, Pål LU
- publishing date
- 2018-02-06
- type
- Contribution to journal
- publication status
- published
- keywords
- Galactosephosphates/metabolism, Glucosephosphates/metabolism, Humans, Phosphoric Diester Hydrolases/metabolism, Protein Folding
- in
- Structure
- volume
- 26
- issue
- 2
- pages
- 6 - 303
- publisher
- Cell Press
- external identifiers
-
- scopus:85041395077
- pmid:29413322
- ISSN
- 0969-2126
- DOI
- 10.1016/j.str.2018.01.004
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2018 Elsevier Ltd. All rights reserved.
- id
- 7c87bba9-4dd6-449c-bcf2-00c74f7c1851
- date added to LUP
- 2019-04-30 07:49:21
- date last changed
- 2024-09-17 18:35:04
@article{7c87bba9-4dd6-449c-bcf2-00c74f7c1851, abstract = {{<p>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.</p>}}, author = {{Carter, Megan and Jemth, Ann-Sofie and Carreras-Puigvert, Jordi and Herr, Patrick and Martínez Carranza, Markel and Vallin, Karl S A and Throup, Adam and Helleday, Thomas and Stenmark, Pål}}, issn = {{0969-2126}}, keywords = {{Galactosephosphates/metabolism; Glucosephosphates/metabolism; Humans; Phosphoric Diester Hydrolases/metabolism; Protein Folding}}, language = {{eng}}, month = {{02}}, number = {{2}}, pages = {{6--303}}, publisher = {{Cell Press}}, series = {{Structure}}, title = {{Human NUDT22 Is a UDP-Glucose/Galactose Hydrolase Exhibiting a Unique Structural Fold}}, url = {{http://dx.doi.org/10.1016/j.str.2018.01.004}}, doi = {{10.1016/j.str.2018.01.004}}, volume = {{26}}, year = {{2018}}, }