2fum

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[[Image:2fum.gif|left|200px]]<br /><applet load="2fum" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2fum, resolution 2.89&Aring;" />
 
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'''Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone'''<br />
 
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==Overview==
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==Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone==
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<StructureSection load='2fum' size='340' side='right'caption='[[2fum]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2fum]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FUM FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MIX:1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE'>MIX</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fum OCA], [https://pdbe.org/2fum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fum RCSB], [https://www.ebi.ac.uk/pdbsum/2fum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fum ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PKNB_MYCTU PKNB_MYCTU] Key component of a signal transduction pathway that regulates cell growth and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, PbpA, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA. Shows a strong preference for Thr versus Ser as the phosphoacceptor.<ref>PMID:15985609</ref> <ref>PMID:15978616</ref> <ref>PMID:15987910</ref> <ref>PMID:16817899</ref> <ref>PMID:16980473</ref> <ref>PMID:16436437</ref> <ref>PMID:19826007</ref> <ref>PMID:19121323</ref> <ref>PMID:20025669</ref> <ref>PMID:21423706</ref> <ref>PMID:22275220</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fu/2fum_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2fum ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Mycobacterium tuberculosis PknB is an essential receptor-like protein kinase involved in cell growth control. Here, we demonstrate that mitoxantrone, an anthraquinone derivative used in cancer therapy, is a PknB inhibitor capable of preventing mycobacterial growth. The structure of the complex reveals that mitoxantrone partially occupies the adenine-binding pocket in PknB, providing a framework for the design of compounds with potential therapeutic applications. PknB crystallizes as a 'back-to-back' homodimer identical to those observed in other structures of PknB in complex with ATP analogs. This organization resembles that of the RNA-dependent protein kinase PKR, suggesting a mechanism for kinase activation in mycobacteria.
Mycobacterium tuberculosis PknB is an essential receptor-like protein kinase involved in cell growth control. Here, we demonstrate that mitoxantrone, an anthraquinone derivative used in cancer therapy, is a PknB inhibitor capable of preventing mycobacterial growth. The structure of the complex reveals that mitoxantrone partially occupies the adenine-binding pocket in PknB, providing a framework for the design of compounds with potential therapeutic applications. PknB crystallizes as a 'back-to-back' homodimer identical to those observed in other structures of PknB in complex with ATP analogs. This organization resembles that of the RNA-dependent protein kinase PKR, suggesting a mechanism for kinase activation in mycobacteria.
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==About this Structure==
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The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria.,Wehenkel A, Fernandez P, Bellinzoni M, Catherinot V, Barilone N, Labesse G, Jackson M, Alzari PM FEBS Lett. 2006 May 29;580(13):3018-22. Epub 2006 Apr 27. PMID:16674948<ref>PMID:16674948</ref>
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2FUM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=MIX:'>MIX</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FUM OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria., Wehenkel A, Fernandez P, Bellinzoni M, Catherinot V, Barilone N, Labesse G, Jackson M, Alzari PM, FEBS Lett. 2006 May 29;580(13):3018-22. Epub 2006 Apr 27. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16674948 16674948]
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</div>
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[[Category: Mycobacterium tuberculosis]]
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<div class="pdbe-citations 2fum" style="background-color:#fffaf0;"></div>
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[[Category: Non-specific serine/threonine protein kinase]]
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== References ==
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[[Category: Single protein]]
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<references/>
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[[Category: Alzari, P M.]]
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__TOC__
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[[Category: Wehenkel, A.]]
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</StructureSection>
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[[Category: MIX]]
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[[Category: Large Structures]]
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[[Category: protein kinase-inhibitor complex]]
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[[Category: Mycobacterium tuberculosis H37Rv]]
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[[Category: Alzari PM]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:25:17 2008''
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[[Category: Wehenkel A]]

Current revision

Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone

PDB ID 2fum

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