Introduction
NudT16 is an archetypical member of the Nudix superfamily of hydrolases. Nudix hydrolases have in common a stretch of 23 amino acids called the Nudix signature sequence which is the binding site for the metal involved in diphosphate hydrolysis. Nudix hydrolases prefer substrates of the form NUcleoside, DIphosphate and X, hence their name NUDIX. Examples of such substrates are ATP where X is PPI, ADPribose where X is phospho-ribose or m7GTP-RNA where X is phospho-RNA. Their catalytic activity hydrolyzes a phosphorus-oxygen bond resulting in a nucleoside monophosphate (NMP) and a phosphate linked to moiety X. While NudT16 was initially described as a nuclear RNA and cytoplasmic mRNA decapping enzyme, further studies have shown that it also effectively hydrolyzes inosine diphosphate (IDP) and its hazardous deoxyribose cognate (dIDP) into inosine monophosphate (IMP) and deoxy inosine monophosphate (dIMP), respectively [1]. NudT16 was shown to hydrolyze ADPribose and polyADPr [2]. Physiologically, NudT16 has 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 (ADPr) from Poly-ADP-ribosylated 53BP1 [3].
Structure
Function
Relevance
References
- ↑ 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. 2015 Jun 29;10(6):e0131507. doi: 10.1371/journal.pone.0131507., eCollection 2015. PMID:26121039 doi:http://dx.doi.org/10.1371/journal.pone.0131507
- ↑ Thirawatananond P, McPherson RL, Malhi J, Nathan S, Lambrecht MJ, Brichacek M, Hergenrother PJ, Leung AKL, Gabelli SB. Structural analyses of NudT16-ADP-ribose complexes direct rational design of mutants with improved processing of poly(ADP-ribosyl)ated proteins. Sci Rep. 2019 Apr 11;9(1):5940. doi: 10.1038/s41598-019-39491-w. PMID:30976021 doi:http://dx.doi.org/10.1038/s41598-019-39491-w
- ↑ Zhang F, Lou L, Peng B, Song X, Reizes O, Almasan A, Gong Z. Nudix Hydrolase NUDT16 Regulates 53BP1 Protein by Reversing 53BP1 ADP-Ribosylation. Cancer Res. 2020 Mar 1;80(5):999-1010. doi: 10.1158/0008-5472.CAN-19-2205. Epub, 2020 Jan 7. PMID:31911551 doi:http://dx.doi.org/10.1158/0008-5472.CAN-19-2205
