5cr7: Difference between revisions
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==Human cytosolic 5'-nucleotidase II in complex with N-(9H-Purin-6-yl)-3-(3-pyrrol-1-ylphenyl)benzamide== | ==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=''> | <StructureSection load='5cr7' size='340' side='right'caption='[[5cr7]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5cr7]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CR7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5cr7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CR7 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cqz|5cqz]], [[4h4b|4h4b]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cqz|5cqz]], [[4h4b|4h4b]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NT5C2, NT5B, NT5CP, PNT5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=5cr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cr7 OCA], [http://pdbe.org/5cr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cr7 RCSB], [http://www.ebi.ac.uk/pdbsum/5cr7 PDBsum]</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=5cr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cr7 OCA], [http://pdbe.org/5cr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cr7 RCSB], [http://www.ebi.ac.uk/pdbsum/5cr7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cr7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: 5'-nucleotidase]] | [[Category: 5'-nucleotidase]] | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Aghajari, N]] | [[Category: Aghajari, N]] | ||
[[Category: Preeti, P]] | [[Category: Preeti, P]] | ||
[[Category: Complex]] | [[Category: Complex]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 14:51, 27 March 2020
Human cytosolic 5'-nucleotidase II in complex with N-(9H-Purin-6-yl)-3-(3-pyrrol-1-ylphenyl)benzamideHuman cytosolic 5'-nucleotidase II in complex with N-(9H-Purin-6-yl)-3-(3-pyrrol-1-ylphenyl)benzamide
Structural highlights
Disease[5NTC_HUMAN] Autosomal recessive spastic paraplegia type 45. The disease is caused by mutations affecting the gene represented in this entry.[1] Function[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. Publication Abstract from PubMedWe 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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