5opl

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'''Unreleased structure'''
 
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The entry 5opl is ON HOLD until Paper Publication
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==Crystal structure of K25E cN-II mutant==
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<StructureSection load='5opl' size='340' side='right'caption='[[5opl]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5opl]] 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=5OPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OPL FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<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></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5opl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5opl OCA], [https://pdbe.org/5opl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5opl RCSB], [https://www.ebi.ac.uk/pdbsum/5opl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5opl ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Activating mutations in NT5C2, a gene encoding cytosolic purine 5'-nucleotidase (cN-II), confer chemoresistance in relapsed acute lymphoblastic leukemia. Here we show that all mutants became independent of allosteric effects of ATP and thus constitutively active. Structural mapping of mutations described in patients demonstrates that 90% of leukemia-specific allelles directly affect two regulatory hotspots within the cN-II molecule-the helix A region: residues 355-365, and the intersubunit interface: helix B (232-242) and flexible interhelical loop L (400-418). Furthermore, analysis of hetero-oligomeric complexes combining wild-type (WT) and mutant subunits showed that the activation is transmitted from the mutated to the WT subunit. This intersubunit interaction forms structural basis of hyperactive NT5C2 in drug-resistant leukemia in which heterozygous NT5C2 mutation gave rise to hetero-tetramer mutant and WT proteins. This enabled us to define criteria to aid the prediction of NT5C2 drug resistance mutations in leukemia.
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Authors: Kugler, M., Hnizda, A., Pachl, P., Rezacova, P.
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Relapsed acute lymphoblastic leukemia-specific mutations in NT5C2 cluster into hotspots driving intersubunit stimulation.,Hnizda A, Fabry M, Moriyama T, Pachl P, Kugler M, Brinsa V, Ascher DB, Carroll WL, Novak P, Zaliova M, Trka J, Rezacova P, Yang JJ, Veverka V Leukemia. 2018 Jun;32(6):1393-1403. doi: 10.1038/s41375-018-0073-5. Epub 2018 Feb, 25. PMID:29535428<ref>PMID:29535428</ref>
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Description: Crystal structure of K25E cN-II mutant
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Hnizda, A]]
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<div class="pdbe-citations 5opl" style="background-color:#fffaf0;"></div>
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[[Category: Pachl, P]]
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== References ==
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[[Category: Rezacova, P]]
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<references/>
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[[Category: Kugler, M]]
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Hnizda A]]
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[[Category: Kugler M]]
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[[Category: Pachl P]]
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[[Category: Rezacova P]]

Current revision

Crystal structure of K25E cN-II mutant

PDB ID 5opl

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