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==STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 36== | |||
<StructureSection load='2xk6' size='340' side='right' caption='[[2xk6]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2xk6]] 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=2XK6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XK6 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EQH:CIS-4-[3-AMINO-6-(3-CYCLOPROPYLTHIOPHEN-2-YL)PYRAZIN-2-YL]CYCLOHEXANECARBOXYLIC+ACID'>EQH</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xkc|2xkc]], [[2w5b|2w5b]], [[2xnp|2xnp]], [[2xk8|2xk8]], [[2wqo|2wqo]], [[2xno|2xno]], [[2jav|2jav]], [[2xnn|2xnn]], [[2xk4|2xk4]], [[2xk3|2xk3]], [[2w5a|2w5a]], [[2xnm|2xnm]], [[2xke|2xke]], [[2xk7|2xk7]], [[2xkd|2xkd]], [[2w5h|2w5h]], [[2xkf|2xkf]]</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 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=2xk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xk6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xk6 RCSB], [http://www.ebi.ac.uk/pdbsum/2xk6 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2. | |||
Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization.,Whelligan DK, Solanki S, Taylor D, Thomson DW, Cheung KM, Boxall K, Mas-Droux C, Barillari C, Burns S, Grummitt CG, Collins I, van Montfort RL, Aherne GW, Bayliss R, Hoelder S J Med Chem. 2010 Oct 11. PMID:20936789<ref>PMID:20936789</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Bayliss, R | [[Category: Bayliss, R]] | ||
[[Category: Mas-Droux, C | [[Category: Mas-Droux, C]] | ||
[[Category: Centrosome]] | [[Category: Centrosome]] | ||
[[Category: Mitosis]] | [[Category: Mitosis]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 14:55, 18 December 2014
STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 36STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 36
Structural highlights
Publication Abstract from PubMedWe report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2. Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization.,Whelligan DK, Solanki S, Taylor D, Thomson DW, Cheung KM, Boxall K, Mas-Droux C, Barillari C, Burns S, Grummitt CG, Collins I, van Montfort RL, Aherne GW, Bayliss R, Hoelder S J Med Chem. 2010 Oct 11. PMID:20936789[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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