NudT16

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Revision as of 16:10, 2 July 2020

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)

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1 Introduction
2 Structure
3 Function

Introduction

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. 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].

Structure

NudT16 is a homodimer, consisting of two monomers of the same sequence. A structure on the left shows one monomer in cyan while the other in purple. This dimerization allows for each subunit to have deeper . Each monomer consists of two beta sheets surrounded by alpha-helices, as is typical of Nudix hydrolases. A variation of the catalytically relevant Nudix box characteristic of Nudix hydrolases consisting of 23 highly conserved residues (G₁Z_2-6E₇Z_8-14R₁₅E₁₆U₁₇Z₁₈E₁₉E₂₀Z₂₁G₂₂U₂₃ where Z is any amino acid and U is an aliphatic and hydrophobic residue) is present in NudT16 (GARRLELGEALALGSGWRHVCHA). In contrast to the negatively charged pockets lined with glutamate residues where metal ligands bind, the adenosine binding pocket is positively charged. The mouth of the binding site is about 9Å in width. Thirawatananond et. al. investigated whether 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]. Many in the mouth of this binding pocket are also involved in hydrogen bonding, the binding of metal ligands, and also serve to delimit the binding site.

Function

Relevance

Nudix enzymes are found in every organism in the three domains of life, signifying the importance of phosphodiester bond hydrolysis. ^[1] 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. [3] ^[2] NudT16 plays a crucial role in the cell cycle as its absence in HeLa MR cells caused cell arrest during the S phase. ^[3]

References

↑ McLennan AG. The Nudix hydrolase superfamily. Cell Mol Life Sci. 2006 Jan;63(2):123-43. doi: 10.1007/s00018-005-5386-7. PMID:16378245 doi:http://dx.doi.org/10.1007/s00018-005-5386-7
↑ 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
↑ Iyama T, Abolhassani N, Tsuchimoto D, Nonaka M, Nakabeppu Y. NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest. Nucleic Acids Res. 2010 Aug;38(14):4834-43. doi: 10.1093/nar/gkq249. Epub 2010, Apr 12. PMID:20385596 doi:http://dx.doi.org/10.1093/nar/gkq249

Proteopedia Page Contributors and Editors (what is this?)

Hannah Campbell, Tihitina Y Aytenfisu, Michal Harel, Sandra B. Gabelli

Retrieved from "http://52.214.119.220/wiki/index.php/NudT16"

@@ Line 15: / Line 15: @@
 </StructureSection>
 == Relevance ==
-ADP ribosylation is a post translational modification that can change various amino acids by conjugating the ADP ribose with the protein.  ADP ribosylation can be reversed by HsNudT16 through hydrolysis of inosine triphosphate or diphosphate. [3]
+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. [3] <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/>

NudT16

From Proteopedia

Revision as of 16:10, 2 July 2020

Contents

Introduction

Structure

Function

Relevance

References

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