2wtj: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wtj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WTJ FirstGlance]. <br> | <table><tr><td colspan='2'>[[2wtj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WTJ FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=WTJ:2-AMINO-5-(2,3-DIHYDROTHIENO[3,4-B][1,4]DIOXIN-5-YL)-N-[2-(DIMETHYLAMINO)ETHYL]PYRIDINE-3-CARBOXAMIDE'>WTJ</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=WTJ:2-AMINO-5-(2,3-DIHYDROTHIENO[3,4-B][1,4]DIOXIN-5-YL)-N-[2-(DIMETHYLAMINO)ETHYL]PYRIDINE-3-CARBOXAMIDE'>WTJ</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wti|2wti]], [[2wtc|2wtc]], [[2wtd|2wtd]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wti|2wti]], [[2wtc|2wtc]], [[2wtd|2wtd]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wtj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wtj RCSB], [http://www.ebi.ac.uk/pdbsum/2wtj 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=2wtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wtj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wtj RCSB], [http://www.ebi.ac.uk/pdbsum/2wtj PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Aherne, G W | [[Category: Aherne, G W]] | ||
[[Category: Allen, C E | [[Category: Allen, C E]] | ||
[[Category: Anderson, V E | [[Category: Anderson, V E]] | ||
[[Category: Antoni, L | [[Category: Antoni, L]] | ||
[[Category: Boxall, K | [[Category: Boxall, K]] | ||
[[Category: Burns, S | [[Category: Burns, S]] | ||
[[Category: Caldwell, J J | [[Category: Caldwell, J J]] | ||
[[Category: Collins, I | [[Category: Collins, I]] | ||
[[Category: Garrett, M D | [[Category: Garrett, M D]] | ||
[[Category: Hilton, S | [[Category: Hilton, S]] | ||
[[Category: Naud, S | [[Category: Naud, S]] | ||
[[Category: Oliver, A W | [[Category: Oliver, A W]] | ||
[[Category: Pearl, L H | [[Category: Pearl, L H]] | ||
[[Category: Cell cycle]] | [[Category: Cell cycle]] | ||
[[Category: Kinase]] | [[Category: Kinase]] | ||
[[Category: Li-fraumeni syndrome]] | [[Category: Li-fraumeni syndrome]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 11:00, 20 January 2015
CRYSTAL STRUCTURE OF CHK2 IN COMPLEX WITH AN INHIBITORCRYSTAL STRUCTURE OF CHK2 IN COMPLEX WITH AN INHIBITOR
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed5-(Hetero)aryl-3-(4-carboxamidophenyl)-2-aminopyridine inhibitors of CHK2 were identified from high throughput screening of a kinase-focussed compound library. Rapid exploration of the hits through straightforward chemistry established structure-activity relationships and a proposed ATP-competitive binding mode which was verified by X-ray crystallography of several analogues bound to CHK2. Variation of the 5-(hetero)aryl substituent identified bicyclic dioxolane and dioxane groups which improved the affinity and the selectivity of the compounds for CHK2 versus CHK1. The 3-(4-carboxamidophenyl) substituent could be successfully replaced by acyclic omega-aminoalkylamides, which made additional polar interactions within the binding site and led to more potent inhibitors of CHK2. Compounds from this series showed activity in cell-based mechanistic assays for inhibition of CHK2. Identification and characterisation of 2-aminopyridine inhibitors of checkpoint kinase 2.,Hilton S, Naud S, Caldwell JJ, Boxall K, Burns S, Anderson VE, Antoni L, Allen CE, Pearl LH, Oliver AW, Wynne Aherne G, Garrett MD, Collins I Bioorg Med Chem. 2010 Jan 15;18(2):707-18. Epub 2009 Dec 6. PMID:20022510[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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