3db6: Difference between revisions
New page: '''Unreleased structure''' The entry 3db6 is ON HOLD until Paper Publication Authors: Elling, R.A., Fucini, R.V., Zhu, J., Barr, K.J., Paulvannan, K., Lew, W., Romanowski, M.J. Descrip... |
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==Crystal structure of an activated (Thr->Asp) Polo-like kinase 1 (Plk1) catalytic domain in complex with Compound 902== | |||
<StructureSection load='3db6' size='340' side='right'caption='[[3db6]], [[Resolution|resolution]] 2.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3db6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DB6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DB6 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]] 2.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRS:1-[5-METHYL-2-(TRIFLUOROMETHYL)FURAN-3-YL]-3-[(2Z)-5-(2-{[6-(1H-1,2,4-TRIAZOL-3-YLAMINO)PYRIMIDIN-4-YL]AMINO}ETHYL)-1,3-THIAZOL-2(3H)-YLIDENE]UREA'>FRS</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=3db6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3db6 OCA], [https://pdbe.org/3db6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3db6 RCSB], [https://www.ebi.ac.uk/pdbsum/3db6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3db6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q4KMI8_DANRE Q4KMI8_DANRE] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/db/3db6_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3db6 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Polo-like kinase 1 (Plk1) is a member of the Polo-like kinase family of serine/threonine kinases involved in the regulation of cell-cycle progression and cytokinesis and is an attractive target for the development of anticancer therapeutics. The catalytic domain of this enzyme shares significant primary amino-acid homology and structural similarity with another mitotic kinase, Aurora A. While screening an Aurora A library of ATP-competitive compounds, a urea-containing inhibitor with low affinity for mouse Aurora A but with submicromolar potency for human and zebrafish Plk1 (hPlk1 and zPlk1, respectively) was identified. A crystal structure of the zebrafish Plk1 kinase domain-inhibitor complex reveals that the small molecule occupies the purine pocket and extends past the catalytic lysine into the adaptive region of the active site. Analysis of the structures of this protein-inhibitor complex and of similar small molecules cocrystallized with other kinases facilitates understanding of the specificity of the inhibitor for Plk1 and documents for the first time that Plk1 can accommodate extended ATP-competitive compounds that project toward the adaptive pocket and help the enzyme order its activation segment. | |||
Structure of the Brachydanio rerio Polo-like kinase 1 (Plk1) catalytic domain in complex with an extended inhibitor targeting the adaptive pocket of the enzyme.,Elling RA, Fucini RV, Hanan EJ, Barr KJ, Zhu J, Paulvannan K, Yang W, Romanowski MJ Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Aug 1;64(Pt, 8):686-91. Epub 2008 Jul 26. PMID:18678933<ref>PMID:18678933</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3db6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Danio rerio]] | |||
[[Category: Large Structures]] | |||
[[Category: Barr KJ]] | |||
[[Category: Elling RA]] | |||
[[Category: Fucini RV]] | |||
[[Category: Romanowski MJ]] | |||
[[Category: Zhu J]] | |||
Latest revision as of 15:44, 30 August 2023
Crystal structure of an activated (Thr->Asp) Polo-like kinase 1 (Plk1) catalytic domain in complex with Compound 902Crystal structure of an activated (Thr->Asp) Polo-like kinase 1 (Plk1) catalytic domain in complex with Compound 902
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPolo-like kinase 1 (Plk1) is a member of the Polo-like kinase family of serine/threonine kinases involved in the regulation of cell-cycle progression and cytokinesis and is an attractive target for the development of anticancer therapeutics. The catalytic domain of this enzyme shares significant primary amino-acid homology and structural similarity with another mitotic kinase, Aurora A. While screening an Aurora A library of ATP-competitive compounds, a urea-containing inhibitor with low affinity for mouse Aurora A but with submicromolar potency for human and zebrafish Plk1 (hPlk1 and zPlk1, respectively) was identified. A crystal structure of the zebrafish Plk1 kinase domain-inhibitor complex reveals that the small molecule occupies the purine pocket and extends past the catalytic lysine into the adaptive region of the active site. Analysis of the structures of this protein-inhibitor complex and of similar small molecules cocrystallized with other kinases facilitates understanding of the specificity of the inhibitor for Plk1 and documents for the first time that Plk1 can accommodate extended ATP-competitive compounds that project toward the adaptive pocket and help the enzyme order its activation segment. Structure of the Brachydanio rerio Polo-like kinase 1 (Plk1) catalytic domain in complex with an extended inhibitor targeting the adaptive pocket of the enzyme.,Elling RA, Fucini RV, Hanan EJ, Barr KJ, Zhu J, Paulvannan K, Yang W, Romanowski MJ Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Aug 1;64(Pt, 8):686-91. Epub 2008 Jul 26. PMID:18678933[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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