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New page: left|200px<br /> <applet load="2dsd" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dsd, resolution 2.60Å" /> '''Crystal structure o... |
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== | ==Crystal structure of human ADP-ribose pyrophosphatase NUDT5 in complex with magnesium and AMP== | ||
Human NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging | <StructureSection load='2dsd' size='340' side='right'caption='[[2dsd]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2dsd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DSD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DSD FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</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'>[https://proteopedia.org/fgij/fg.htm?mol=2dsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dsd OCA], [https://pdbe.org/2dsd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dsd RCSB], [https://www.ebi.ac.uk/pdbsum/2dsd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dsd ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NUDT5_HUMAN NUDT5_HUMAN] Hydrolyzes with similar activities ADP-ribose ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP. Can also hydrolyze other nucleotide sugars with low activity.<ref>PMID:17052728</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ds/2dsd_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2dsd ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging to the Nudix hydrolase superfamily. It presumably plays important roles in controlling the intracellular level of ADP-ribose (ADPR) to prevent non-enzymatic ADP-ribosylation by hydrolyzing ADPR to AMP and ribose 5'-phosphate. We report here the crystal structures of hNUDT5 in apo form, in complex with ADPR, and in complex with AMP with bound Mg2+. hNUDT5 forms a homodimer with substantial domain swapping and assumes a structure more similar to Escherichia coli ADPRase ORF209 than human ADPRase NUDT9. The adenine moiety of the substrates is specifically recognized by the enzyme via hydrogen-bonding interactions between N1 and N6 of the base and Glu47 of one subunit, and between N7 of the base and Arg51 of the other subunit, providing the molecular basis for the high selectivity of hNUDT5 for ADP-sugars over other sugar nucleotides. Structural comparisons with E. coli ADPRase ORF209 and ADPXase ORF186 indicate that the existence of an aromatic residue on loop L8 in ORF186 seems to be positively correlated with its enzymatic activity on APnA, whereas hNUDT5 and ORF209 contain no such residue and thus have low or no activities on APnA. | |||
Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.,Zha M, Zhong C, Peng Y, Hu H, Ding J J Mol Biol. 2006 Dec 15;364(5):1021-33. Epub 2006 Oct 3. PMID:17052728<ref>PMID:17052728</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 2dsd" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[ADP-ribose pyrophosphatase 3D structures|ADP-ribose pyrophosphatase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Ding | [[Category: Ding J]] | ||
[[Category: Zha | [[Category: Zha M]] | ||
[[Category: Zhong | [[Category: Zhong C]] | ||
Latest revision as of 11:29, 25 October 2023
Crystal structure of human ADP-ribose pyrophosphatase NUDT5 in complex with magnesium and AMPCrystal structure of human ADP-ribose pyrophosphatase NUDT5 in complex with magnesium and AMP
Structural highlights
FunctionNUDT5_HUMAN Hydrolyzes with similar activities ADP-ribose ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP. Can also hydrolyze other nucleotide sugars with low activity.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging to the Nudix hydrolase superfamily. It presumably plays important roles in controlling the intracellular level of ADP-ribose (ADPR) to prevent non-enzymatic ADP-ribosylation by hydrolyzing ADPR to AMP and ribose 5'-phosphate. We report here the crystal structures of hNUDT5 in apo form, in complex with ADPR, and in complex with AMP with bound Mg2+. hNUDT5 forms a homodimer with substantial domain swapping and assumes a structure more similar to Escherichia coli ADPRase ORF209 than human ADPRase NUDT9. The adenine moiety of the substrates is specifically recognized by the enzyme via hydrogen-bonding interactions between N1 and N6 of the base and Glu47 of one subunit, and between N7 of the base and Arg51 of the other subunit, providing the molecular basis for the high selectivity of hNUDT5 for ADP-sugars over other sugar nucleotides. Structural comparisons with E. coli ADPRase ORF209 and ADPXase ORF186 indicate that the existence of an aromatic residue on loop L8 in ORF186 seems to be positively correlated with its enzymatic activity on APnA, whereas hNUDT5 and ORF209 contain no such residue and thus have low or no activities on APnA. Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.,Zha M, Zhong C, Peng Y, Hu H, Ding J J Mol Biol. 2006 Dec 15;364(5):1021-33. Epub 2006 Oct 3. PMID:17052728[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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