1q33: Difference between revisions
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==Crystal structure of human ADP-ribose pyrophosphatase NUDT9== | |||
<StructureSection load='1q33' size='340' side='right'caption='[[1q33]], [[Resolution|resolution]] 1.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1q33]] is a 1 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=1Q33 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q33 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]] 1.81Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1q33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q33 OCA], [https://pdbe.org/1q33 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q33 RCSB], [https://www.ebi.ac.uk/pdbsum/1q33 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q33 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NUDT9_HUMAN NUDT9_HUMAN] Hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate. | |||
== 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/q3/1q33_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1q33 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human ADP-ribose pyrophosphatase NUDT9 belongs to a superfamily of Nudix hydrolases that catabolize potentially toxic compounds in the cell. The enzyme hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate. NUDT9 shares 39% sequence identity with the C-terminal cytoplasmic domain of the ADPR-gated calcium channel TRPM2, which exhibits low but specific enzyme activity. We determined crystal structures of NUDT9 in the presence and in the absence of the reaction product ribose 5'-phosphate. On the basis of these structures and comparison with a bacterial homologue, a model of the substrate complex was built. The structure and activity of a double point mutant (R(229)E(230)F(231) to R(229)I(230)L(231)), which mimics the Nudix signature of the ion channel domain, was determined. Finally, the activities of a pair of additional mutated constructs were compared to the wild-type enzyme. The first corresponds to a minimal Nudix domain missing an N-terminal domain and C-terminal tail; the second disrupts two potential general bases in the active site. NUDT9 contains an N-terminal domain with a novel fold and a catalytic C-terminal Nudix domain. Unlike its closest functional homologue (homodimeric Escherichia coli ADPRase), it is active as a monomer, and the substrate is bound in a cleft between the domains. The structure of the RIL mutant provides structural basis for the reduced activity of the TRPM2 ion channel. The conformation and binding interactions of ADPR substrate are predicted to differ from those observed for E.coli ADPRase; mutation of structurally aligned acidic residues in their active sites produce significantly different effects on catalytic efficiency, indicating that their reaction pathways and mechanisms may have diverged. | |||
The crystal structure and mutational analysis of human NUDT9.,Shen BW, Perraud AL, Scharenberg A, Stoddard BL J Mol Biol. 2003 Sep 12;332(2):385-98. PMID:12948489<ref>PMID:12948489</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1q33" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[ADP-ribose pyrophosphatase|ADP-ribose pyrophosphatase]] | *[[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: | [[Category: Perraud AL]] | ||
[[Category: | [[Category: Scharenberg A]] | ||
[[Category: | [[Category: Shen BW]] | ||
[[Category: | [[Category: Stoddard BL]] | ||
Latest revision as of 10:14, 30 October 2024
Crystal structure of human ADP-ribose pyrophosphatase NUDT9Crystal structure of human ADP-ribose pyrophosphatase NUDT9
Structural highlights
FunctionNUDT9_HUMAN Hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate. 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 ADP-ribose pyrophosphatase NUDT9 belongs to a superfamily of Nudix hydrolases that catabolize potentially toxic compounds in the cell. The enzyme hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate. NUDT9 shares 39% sequence identity with the C-terminal cytoplasmic domain of the ADPR-gated calcium channel TRPM2, which exhibits low but specific enzyme activity. We determined crystal structures of NUDT9 in the presence and in the absence of the reaction product ribose 5'-phosphate. On the basis of these structures and comparison with a bacterial homologue, a model of the substrate complex was built. The structure and activity of a double point mutant (R(229)E(230)F(231) to R(229)I(230)L(231)), which mimics the Nudix signature of the ion channel domain, was determined. Finally, the activities of a pair of additional mutated constructs were compared to the wild-type enzyme. The first corresponds to a minimal Nudix domain missing an N-terminal domain and C-terminal tail; the second disrupts two potential general bases in the active site. NUDT9 contains an N-terminal domain with a novel fold and a catalytic C-terminal Nudix domain. Unlike its closest functional homologue (homodimeric Escherichia coli ADPRase), it is active as a monomer, and the substrate is bound in a cleft between the domains. The structure of the RIL mutant provides structural basis for the reduced activity of the TRPM2 ion channel. The conformation and binding interactions of ADPR substrate are predicted to differ from those observed for E.coli ADPRase; mutation of structurally aligned acidic residues in their active sites produce significantly different effects on catalytic efficiency, indicating that their reaction pathways and mechanisms may have diverged. The crystal structure and mutational analysis of human NUDT9.,Shen BW, Perraud AL, Scharenberg A, Stoddard BL J Mol Biol. 2003 Sep 12;332(2):385-98. PMID:12948489[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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