Structural Basis for the Specificity of Human NUDT16 and Its Regulation by Inosine Monophosphate.

ABSTRACT: Human NUDT16 is a member of the NUDIX hydrolase superfamily. After having been initially described as an mRNA decapping enzyme, recent studies conferred it a role as an "housecleaning" enzyme specialized in the removal of hazardous (deoxy)inosine diphosphate from the nucleotide pool. Here we present the crystal structure of human NUDT16 both in its apo-form and in complex with its product inosine monophosphate (IMP). NUDT16 appears as a dimer whose formation generates a positively charged trench to accommodate substrate-binding. Complementation of the structural data with detailed enzymatic and biophysical studies revealed the determinants of substrate recognition and particularly the importance of the substituents in position 2 and 6 on the purine ring. The affinity for the IMP product, h

SUBMITTER: Tresaugues L 

PROVIDER: S-EPMC4485890 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature