5cr7: Difference between revisions
New page: '''Unreleased structure''' The entry 5cr7 is ON HOLD until sometime in the future Authors: Aghajari, N., Preeti, P. Description: Human cytosolic 5'-nucleotidase II in complex with N-(9... |
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The entry | ==Human cytosolic 5'-nucleotidase II in complex with N-(9H-Purin-6-yl)-3-(3-pyrrol-1-ylphenyl)benzamide== | ||
<StructureSection load='5cr7' size='340' side='right'caption='[[5cr7]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5cr7]] 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=5CR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CR7 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]] 2.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5WO:~{N}-(7~{H}-PURIN-6-YL)-3-(3-PYRROL-1-YLPHENYL)BENZAMIDE'>5WO</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5cr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cr7 OCA], [https://pdbe.org/5cr7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cr7 RCSB], [https://www.ebi.ac.uk/pdbsum/5cr7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cr7 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. | |||
<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> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5cr7" style="background-color:#fffaf0;"></div> | ||
[[Category: Aghajari | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Aghajari N]] | |||
[[Category: Preeti P]] | |||