NudT16

IntroductionIntroduction

NudT16 is a member of the Nudix superfamily of hydrolases which break a phosphoester bond between the two phosphates in nucleoside diphosphate-linked to moiety X proteins resulting in a nucleoside monophosphate (NMP) and a phosphate linked to moiety X. Nudix hydrolases are characterized by a catalytically relevant Nudix box consisting of 23 highly conserved residues (G1Z2-6E7Z8-14R15E16U17Z18E19E20Z21G22U23 where Z is any amino acid and U is an aliphatic and hydrophobic residue). While NudT16 was initially described as a nuclear RNA and cytoplasmic mRNA decapping enzyme, further studies have shown that it also effectively hydrolyzes inosine diphsophate (IDP) and its hazardous deoxyribose cognate (dIDP) into inosine monophsophate (IMP) and deoxy inosine monophosphate (dIMP), respectively [1]. NudT16 has also been shown to regulate levels of 53BP1, an adaptor protein that recruits other proteins to the site of a DNA breakage, through hydrolytic removal of ADP-ribose from ADP-ribosylated 53BP1 [2].

StructureStructure

NudT16 is a homodimer, one monomer is shown in cyan while the other is shown in purple. This bonding together of the two subunits allows for the protein to have a deeper binding pocket. The pocket where the adenosine binds is positively charged as opposed to the negatively charged pockets lined with glutamate residues where metal ligands bind. The mouth of the binding site is about 9 Angstroms in width, widening of this mouth would allow proteins conjugated to ADP further into the binding site. Contrary to Nudix ADPRases, HsNudT16 binds adenosine of ADPr and buries it deep in the core, while leaving the non-adenosine ribose exposed to the surface. This orientation allows the exposed ribose to conjugate another protein[3].

Anything in this section will appear adjacent to the 3D structure and will be scrollable.

spinqualitylabelsall models Crystal structure of HsNUDT16 in complex with diADPR, one monomer is shown in cyan with amino acids 4-17 in blue, the other monomer is shown in purple and has residues 3-17 colored in pink. (PDB entry 6B09) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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