2xsq

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Revision as of 13:30, 19 April 2017

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

Structural highlights

2xsq is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NUD16_HUMAN] RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. Part of the U8 snoRNP complex that is required for the accumulation of mature 5.8S and 28S rRNA. Has diphosphatase activity and removes m7G and/or m227G caps from U8 snoRNA and leaves a 5'monophosphate on the RNA. Catalyzes also the cleavage of the cap structure on mRNAs. Does not hydrolyze cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG). Also hydrolysis m7G- and m227G U3-capped RNAs but with less efficiencies. Has broad substrate specificity with manganese or cobalt as cofactor and can act on various RNA species. Binds to the U8 snoRNA; metal is not required for RNA-binding. May play a role in the regulation of snoRNAs and mRNAs degradation. Acts also as a phosphatase; hydrolyzes the non-canonical purine nucleotides inosine diphosphate (IDP) and deoxyinosine diphosphate (dITP) as well as guanosine diphosphate (GDP), deoxyguanosine diphosphate (dGDP), xanthine diphosphate (XDP), inosine triphosphate (ITP) and deoxyinosine triphosphate (ITP) to their respective monophosphate derivatives and does not distinguish between the deoxy- and ribose forms. The order of activity with different substrates is IDP > dIDP >> GDP = dGDP > XDP = ITP = dITP. Binds strongly to GTP, ITP and XTP. Participates in the hydrolysis of dIDP/IDP and probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.

Publication Abstract from PubMed

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.

Structural Basis for the Specificity of Human NUDT16 and Its Regulation by Inosine Monophosphate.,Tresaugues L, Lundback T, Welin M, Flodin S, Nyman T, Silvander C, Graslund S, Nordlund P PLoS One. 2015 Jun 29;10(6):e0131507. doi: 10.1371/journal.pone.0131507., eCollection 2015. PMID:26121039^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2xsq"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human Nudix motif 16 (NUDT16) in complex with IMP and magnesium==
 <StructureSection load='2xsq' size='340' side='right' caption='[[2xsq]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2xsq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XSQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XSQ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xsq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xsq RCSB], [http://www.ebi.ac.uk/pdbsum/2xsq PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xsq OCA], [http://pdbe.org/2xsq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xsq RCSB], [http://www.ebi.ac.uk/pdbsum/2xsq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xsq ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2xsq" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2xsq

From Proteopedia

Revision as of 13:30, 19 April 2017

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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