5cqz
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5cqz is ON HOLD Authors: Preeti, P., Aghajari, N. Description: Human cytosolic 5'-nucleotidase II in complex with 3-(3-Imidazol-1-ylphenyl)-N-(9H-p...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Human cytosolic 5'-nucleotidase II in complex with 3-(3-Imidazol-1-ylphenyl)-N-(9H-purin-6-yl)benzamide== | |
| + | <StructureSection load='5cqz' size='340' side='right' caption='[[5cqz]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5cqz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CQZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CQZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=53O:1-(BIPHENYL-3-YL)-1H-IMIDAZOLE'>53O</scene>, <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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4h4b|4h4b]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5'-nucleotidase 5'-nucleotidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.5 3.1.3.5] </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=5cqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cqz OCA], [http://pdbe.org/5cqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cqz RCSB], [http://www.ebi.ac.uk/pdbsum/5cqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cqz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://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 == | ||
| + | [[http://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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We used a combined approach based on fragment-based drug design (FBDD) and in silico methods to design potential inhibitors of the cytosolic 5'-nucleotidase II (cN-II), which has been recognized as an important therapeutic target in hematological cancers. Two subgroups of small compounds (including adenine and biaryl moieties) were identified as cN-II binders and a fragment growing strategy guided by molecular docking was considered. Five compounds induced a strong inhibition of the 5'-nucleotidase activity in vitro, and the most potent ones were characterized as noncompetitive inhibitors. Biological evaluation in cancer cell lines showed synergic effect with selected anticancer drugs. Structural studies using X-ray crystallography lead to the identification of new binding sites for two derivatives and of a new crystal form showing important domain swapping. Altogether, the strategy developed herein allowed identifying new original noncompetitive inhibitors against cN-II that act in a synergistic manner with well-known antitumoral agents. | ||
| - | + | Identification of Noncompetitive Inhibitors of Cytosolic 5'-Nucleotidase II Using a Fragment-Based Approach.,Marton Z, Guillon R, Krimm I, Preeti, Rahimova R, Egron D, Jordheim LP, Aghajari N, Dumontet C, Perigaud C, Lionne C, Peyrottes S, Chaloin L J Med Chem. 2015 Dec 24;58(24):9680-96. doi: 10.1021/acs.jmedchem.5b01616. Epub, 2015 Dec 7. PMID:26599519<ref>PMID:26599519</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5cqz" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: 5'-nucleotidase]] | ||
[[Category: Aghajari, N]] | [[Category: Aghajari, N]] | ||
| + | [[Category: Preeti, P]] | ||
| + | [[Category: Cn-ii]] | ||
| + | [[Category: High km 5-prime nucleotidase]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Hydrolase-hydrolase effector complex]] | ||
| + | [[Category: Nucleotide-binding]] | ||
| + | [[Category: Phosphoprotein]] | ||
Current revision
Human cytosolic 5'-nucleotidase II in complex with 3-(3-Imidazol-1-ylphenyl)-N-(9H-purin-6-yl)benzamide
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