2jrh

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[[Image:2jrh.jpg|left|200px]]<br /><applet load="2jrh" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2jrh" />
 
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'''Solution sturcture of human MEKK3 PB1 domain cis isomer'''<br />
 
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==Overview==
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==Solution structure of human MEKK3 PB1 domain cis isomer==
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MEKK3 is a mitogen-activated protein kinase kinase kinase that, participates in various signaling pathways. One of its functions is to, activate the ERK5 signal pathway by phosphorylating and activating MEK5., MEKK3 and MEK5 each harbors a PB1 domain in the N-terminus, and they form, a heterodimer via PB1-PB1 domain interaction that was reported to be, indispensable to the activation of MEK5. Using NMR spectroscopy, we show, here that a prolyl isomerization of the Gln38-Pro39 bond is present in, MEKK3 PB1, which is the first case of structural heterogeneity within PB1, domains. We have solved the solution structures of both isomers and found, a major difference between them in the Pro39 region. Residues Gly37-Leu40, form a type VIb beta-turn in the cis conformation, whereas no obvious, character of beta-turn was observed in the trans conformation. Backbone, dynamics studies have unraveled internal motions in the beta3/beta4-turn, on a microsecond-millisecond time scale. Further investigation of its, binding properties with MEK5 PB1 has demonstrated that MEKK3 PB1 binds, MEK5 PB1 tightly with a Kd of about 10-8 M. Mutagenesis analysis revealed, that residues in the basic cluster of MEKK3 PB1 contributes differently to, the PB1-PB1 interaction. Residues Lys 7 and Arg 5 play important roles in, the interaction with MEK5 PB1. Taken together, this study provides new, insights into structural details of MEKK3 PB1 and its binding properties, with MEK5 PB1.
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<StructureSection load='2jrh' size='340' side='right'caption='[[2jrh]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2jrh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JRH 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">Solution NMR</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=2jrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jrh OCA], [https://pdbe.org/2jrh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jrh RCSB], [https://www.ebi.ac.uk/pdbsum/2jrh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jrh ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/M3K3_HUMAN M3K3_HUMAN] Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.<ref>PMID:9006902</ref> <ref>PMID:12912994</ref> <ref>PMID:14661019</ref> <ref>PMID:14743216</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/jr/2jrh_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=2jrh 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 ==
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MEKK3 is a mitogen-activated protein kinase kinase kinase that participates in various signaling pathways. One of its functions is to activate the ERK5 signal pathway by phosphorylating and activating MEK5. MEKK3 and MEK5 each harbors a PB1 domain in the N-terminus, and they form a heterodimer via PB1-PB1 domain interaction that was reported to be indispensable to the activation of MEK5. Using NMR spectroscopy, we show here that a prolyl isomerization of the Gln38-Pro39 bond is present in MEKK3 PB1, which is the first case of structural heterogeneity within PB1 domains. We have solved the solution structures of both isomers and found a major difference between them in the Pro39 region. Residues Gly37-Leu40 form a type VIb beta-turn in the cis conformation, whereas no obvious character of beta-turn was observed in the trans conformation. Backbone dynamics studies have unraveled internal motions in the beta3/beta4-turn on a microsecond-millisecond time scale. Further investigation of its binding properties with MEK5 PB1 has demonstrated that MEKK3 PB1 binds MEK5 PB1 tightly with a Kd of about 10(-8) M. Mutagenesis analysis revealed that residues in the basic cluster of MEKK3 PB1 contributes differently to the PB1-PB1 interaction. Residues Lys 7 and Arg 5 play important roles in the interaction with MEK5 PB1. Taken together, this study provides new insights into structural details of MEKK3 PB1 and its binding properties with MEK5 PB1.
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==About this Structure==
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Insight into the binding properties of MEKK3 PB1 to MEK5 PB1 from its solution structure.,Hu Q, Shen W, Huang H, Liu J, Zhang J, Huang X, Wu J, Shi Y Biochemistry. 2007 Nov 27;46(47):13478-89. Epub 2007 Nov 7. PMID:17985933<ref>PMID:17985933</ref>
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2JRH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JRH 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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Insight into the Binding Properties of MEKK3 PB1 to MEK5 PB1 from Its Solution Structure(,)., Hu Q, Shen W, Huang H, Liu J, Zhang J, Huang X, Wu J, Shi Y, Biochemistry. 2007 Nov 27;46(47):13478-89. Epub 2007 Nov 7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17985933 17985933]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2jrh" style="background-color:#fffaf0;"></div>
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[[Category: Mitogen-activated protein kinase kinase kinase]]
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[[Category: Single protein]]
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[[Category: Jiahai, Z.]]
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[[Category: Jihui, W.]]
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[[Category: Qi, H.]]
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[[Category: Yunyu, S.]]
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[[Category: kinase signaling domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:01:40 2008''
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==See Also==
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*[[Mitogen-activated protein kinase kinase kinase|Mitogen-activated protein kinase kinase kinase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Jiahai Z]]
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[[Category: Jihui W]]
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[[Category: Qi H]]
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[[Category: Yunyu S]]

Current revision

Solution structure of human MEKK3 PB1 domain cis isomer

PDB ID 2jrh

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