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== | ==Crystal structure of Human Cytosolic 5'-Nucleotidase II (NT5C2, cN-II)== | ||
Cytosolic 5'-nucleotidase II catalyzes the dephosphorylation of | <StructureSection load='2j2c' size='340' side='right'caption='[[2j2c]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2j2c]] 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=2J2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J2C 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]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2j2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j2c OCA], [https://pdbe.org/2j2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j2c RCSB], [https://www.ebi.ac.uk/pdbsum/2j2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j2c ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/5NTC_HUMAN 5NTC_HUMAN] Autosomal recessive spastic paraplegia type 45. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:24482476</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/5NTC_HUMAN 5NTC_HUMAN] May have a critical role in the maintenance of a constant composition of intracellular purine/pyrimidine nucleotides in cooperation with other nucleotidases. Preferentially hydrolyzes inosine 5'-monophosphate (IMP) and other purine nucleotides. | |||
== 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/j2/2j2c_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=2j2c ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cytosolic 5'-nucleotidase II catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates and regulates the IMP and GMP pools within the cell. It possesses phosphotransferase activity and thereby also catalyzes the reverse reaction. Both reactions are allosterically activated by adenine-based nucleotides and 2,3-bisphosphoglycerate. We have solved structures of cytosolic 5'-nucleotidase II as native protein (2.2 Angstrom) and in complex with adenosine (1.5 Angstrom) and beryllium trifluoride (2.15 Angstrom) The tetrameric enzyme is structurally similar to enzymes of the haloacid dehalogenase (HAD) superfamily, including mitochondrial 5'(3')-deoxyribonucleotidase and cytosolic 5'-nucleotidase III but possesses additional regulatory regions that contain two allosteric effector sites. At effector site 1 located near a subunit interface we modeled diadenosine tetraphosphate with one adenosine moiety in each subunit. This efficiently glues the tetramer subunits together in pairs. The model shows why diadenosine tetraphosphate but not diadenosine triphosphate activates the enzyme and supports a role for cN-II during apoptosis when the level of diadenosine tetraphosphate increases. We have also modeled 2,3-bisphosphoglycerate in effector site 1 using one phosphate site from each subunit. By comparing the structure of cytosolic 5'-nucleotidase II with that of mitochondrial 5'(3')-deoxyribonucleotidase in complex with dGMP, we identified residues involved in substrate recognition. | |||
Crystal structure of human cytosolic 5'-nucleotidase II: insights into allosteric regulation and substrate recognition.,Wallden K, Stenmark P, Nyman T, Flodin S, Graslund S, Loppnau P, Bianchi V, Nordlund P J Biol Chem. 2007 Jun 15;282(24):17828-36. Epub 2007 Apr 3. PMID:17405878<ref>PMID:17405878</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2j2c" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith C]] | ||
[[Category: Berglund H]] | |||
[[Category: Berglund | [[Category: Busam R]] | ||
[[Category: Busam | [[Category: Collins R]] | ||
[[Category: Collins | [[Category: Edwards A]] | ||
[[Category: Edwards | [[Category: Ehn M]] | ||
[[Category: Ehn | [[Category: Flodin S]] | ||
[[Category: Flodin | [[Category: Flores A]] | ||
[[Category: Flores | [[Category: Graslund S]] | ||
[[Category: Graslund | [[Category: Hallberg BM]] | ||
[[Category: Hallberg | [[Category: Hammarstrom M]] | ||
[[Category: Hammarstrom | [[Category: Hogbom M]] | ||
[[Category: Hogbom | [[Category: Holmberg Schiavone L]] | ||
[[Category: Karlberg | [[Category: Karlberg T]] | ||
[[Category: Kotenyova | [[Category: Kotenyova T]] | ||
[[Category: Loppnau | [[Category: Loppnau P]] | ||
[[Category: Magnusdottir | [[Category: Magnusdottir A]] | ||
[[Category: Nilsson-Ehle | [[Category: Nilsson-Ehle P]] | ||
[[Category: Nordlund | [[Category: Nordlund P]] | ||
[[Category: Nyman | [[Category: Nyman T]] | ||
[[Category: Ogg | [[Category: Ogg D]] | ||
[[Category: Persson | [[Category: Persson C]] | ||
[[Category: Sagemark | [[Category: Sagemark J]] | ||
[[Category: Stenmark P]] | |||
[[Category: Stenmark | [[Category: Sundstrom M]] | ||
[[Category: Sundstrom | [[Category: Thorsell AG]] | ||
[[Category: Thorsell | [[Category: Uppenberg J]] | ||
[[Category: Uppenberg | [[Category: Van Den Berg S]] | ||
[[Category: | [[Category: Wallden K]] | ||
[[Category: | [[Category: Weigelt J]] | ||
[[Category: | [[Category: Welin M]] | ||
[[Category: | |||