A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family.

ABSTRACT: The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, e

SUBMITTER: Carreras-Puigvert J 

PROVIDER: S-EPMC5688067 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature