2XSQ

Crystal structure of human Nudix motif 16 (NUDT16) in complex with IMP and magnesium

Summary for 2XSQ

• Entry DOI: 10.2210/pdb2xsq/pdb
• Descriptor: U8 SNORNA-DECAPPING ENZYME, INOSINIC ACID, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase, mrna decapping, mrna turnover, structural genomics consortium, sgc
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : Q96DE0
• Total number of polymer chains: 1
• Total formula weight: 24321.45

Authors

Tresaugues, L.,Welin, M.,Arrowsmith, C.H.,Berglund, H.,Bountra, C.,Collins, R.,Edwards, A.M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Johansson, I.,Karlberg, T.,Kol, S.,Kotenyova, T.,Kouznetsova, E.,Moche, M.,Nyman, T.,Persson, C.,Schuler, H.,Schutz, P.,Siponen, M.I.,Thorsell, A.G.,van den Berg, S.,Wahlberg, E.,Weigelt, J.,Nordlund, P. (deposition date: 2010-09-29, release date: 2010-11-17, Last modification date: 2023-12-20)

Primary citation

Tresaugues, L.,Lundback, T.,Welin, M.,Flodin, S.,Nyman, T.,Silvander, C.,Graslund, S.,Nordlund, P.
Structural Basis for the Specificity of Human Nudt16 and its Regulation by Inosine Monophosphate.
Plos One, 10:31507-, 2015

PubMed 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, harboring a carbonyl in position 6 on the base, compared to purine monophosphates lacking a H-bond acceptor in this position, implies a catalytic cycle whose rate is primarily regulated by the product-release step. Finally, we have also characterized a phenomenon of inhibition by the product of the reaction, IMP, which might exclude non-deleterious nucleotides from NUDT16-mediated hydrolysis regardless of their cellular concentration. Taken together, this study details structural and regulatory mechanisms explaining how substrates are selected for hydrolysis by human NUDT16.

PubMed: 26121039
DOI: 10.1371/JOURNAL.PONE.0131507

Experimental method

X-RAY DIFFRACTION (1.72 Å)