NudT16: Difference between revisions
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<StructureSection load='6B09' size='350' side='right' caption='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]])' scene='84/849734/Nudt16/5'> | <StructureSection load='6B09' size='350' side='right' caption='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]])' scene='84/849734/Nudt16/5'> | ||
__TOC__ | __TOC__</StructureSection> | ||
==Introduction== | ==Introduction== | ||
'''NudT16''' is a member of the Nudix superfamily of hydrolases which breaks a phosphorus-oxygen bond between the two phosphates in nucleoside diphosphate-linked to moiety X molecules 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 <ref>PMID: 26121039</ref>. 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 (ADPr) from Poly-ADP-ribosylated 53BP1 <ref>PMID: 31911551</ref>. | '''NudT16''' is a member of the Nudix superfamily of hydrolases which breaks a phosphorus-oxygen bond between the two phosphates in nucleoside diphosphate-linked to moiety X molecules 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 <ref>PMID: 26121039</ref>. 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 (ADPr) from Poly-ADP-ribosylated 53BP1 <ref>PMID: 31911551</ref>. | ||
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Thirawatananond et. al. investigated whether the widening of the ADPr binding site would allow for increased hydrolysis activity by NudT16. The group designed such mutants (F36A, F61S, and a double mutant with both F36A and F61S) and found that for these mutants, NudT16 hydrolysis activity decreased in free ADPr, remained comparably efficient in mono(ADP-ribosylated) proteins, and increased in poly(ADP-ribosylated) proteins. <ref>PMID: 30976021</ref> | Thirawatananond et. al. investigated whether the widening of the ADPr binding site would allow for increased hydrolysis activity by NudT16. The group designed such mutants (F36A, F61S, and a double mutant with both F36A and F61S) and found that for these mutants, NudT16 hydrolysis activity decreased in free ADPr, remained comparably efficient in mono(ADP-ribosylated) proteins, and increased in poly(ADP-ribosylated) proteins. <ref>PMID: 30976021</ref> | ||
NudT16 is a (Deoxy)inosine diphosphatase. Iyama et. al. found that HsNudT16 binds strongly to GTP, ITP, and XTP. The loss of this protein is followed by increased accumulation of single-strand breaks in DNA, reduced proliferation, and increased cell arrest. They also found increased levels of inosine in RNA, which informed the conclusion that HsNudT16 functions in the nucleus to protect the cell from ITP and its detrimental effects. <ref>PMID:20385596</ref> | NudT16 is a (Deoxy)inosine diphosphatase. Iyama et. al. found that HsNudT16 binds strongly to GTP, ITP, and XTP. The loss of this protein is followed by increased accumulation of single-strand breaks in DNA, reduced proliferation, and increased cell arrest. They also found increased levels of inosine in RNA, which informed the conclusion that HsNudT16 functions in the nucleus to protect the cell from ITP and its detrimental effects. <ref>PMID:20385596</ref> | ||
== Relevance == | == Relevance == | ||
Nudix enzymes are found in every organism in the three domains of life, signifying the importance of phosphodiester bond hydrolysis. <ref>PMID: 16378245</ref> | Nudix enzymes are found in every organism in the three domains of life, signifying the importance of phosphodiester bond hydrolysis. <ref>PMID: 16378245</ref> | ||
One of the most biologically important processes NudT16 plays a role in is ADP ribosylation, a post-translational modification that can change various amino acids by conjugating the ADP ribose with the protein. HsNudT16 can reverse ADP ribosylation through hydrolysis of inosine triphosphate or diphosphate. | One of the most biologically important processes NudT16 plays a role in is ADP ribosylation, a post-translational modification that can change various amino acids by conjugating the ADP ribose with the protein. HsNudT16 can reverse ADP ribosylation through hydrolysis of inosine triphosphate or diphosphate. <ref>PMID: 30976021</ref> NudT16 plays a crucial role in the cell cycle as its absence in HeLa MR cells caused cell arrest during the S phase. <ref>PMID: 20385596</ref> | ||
== References == | == References == | ||
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