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

Carter M, Jemth AS, Carreras-Puigvert J, Herr P, Martínez Carranza M, Vallin KSA, Throup A, Helleday T, Stenmark P

Structure 26 (2) 295-303.e6 [2018-02-06; online 2018-02-08]

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.

Protein Science Facility (PSF) [Service]

PubMed 29413322

DOI 10.1016/j.str.2018.01.004

Crossref 10.1016/j.str.2018.01.004

pii: S0969-2126(18)30004-2

Publications 9.5.0