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1nmw

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[[Image:1nmw.gif|left|200px]]<br /><applet load="1nmw" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1nmw" />
 
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'''Solution structure of the PPIase domain of human Pin1'''<br />
 
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==Overview==
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==Solution structure of the PPIase domain of human Pin1==
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The peptidyl-prolyl cis/trans isomerase hPin1 is a phosphorylation-dependent regulatory enzyme whose substrates are proteins involved in regulation of cell cycle, transcription, Alzheimer's disease, and cancer pathogenesis. We have determined the solution structure of the two domain protein hPin1-(1-163) and its separately expressed PPIase domain (50-163) (hPin1PPIase) with an root mean square deviation of &lt;0.5 A over backbone atoms using NMR. Domain organization of hPin1 differs from that observed in structures solved by x-ray crystallography. Whereas PPIase and WW domain are tightly packed onto each other and share a common binding interface in crystals, our NMR-based data revealed only weak interaction of both domains at their interface in solution. Interaction between the two domains of full-length hPin1 is absent when the protein is dissected into the catalytic and the WW domain. It indicates that the flexible linker, connecting both domains, promotes binding. By evaluation of NOESY spectra we can show that the alpha1/beta1 loop, which was proposed to undergo a large conformational rearrangement in the absence of sulfate and an Ala-Pro peptide, remained in the closed conformation under these conditions. Dissociation constants of 0.4 and 2.0 mm for sulfate and phosphate ions were measured at 12 degrees C by fluorescence spectroscopy. Binding of sulfate prevents hPin1 aggregation and changes surface charges across the active center and around the reactive and catalytically essential Cys113. In the absence of sulfate and/or reducing agent this residue seems to promote aggregation, as observed in hPin1 solutions in vitro.
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<StructureSection load='1nmw' size='340' side='right'caption='[[1nmw]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nmw]] 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=1NMW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NMW 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1nmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nmw OCA], [https://pdbe.org/1nmw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nmw RCSB], [https://www.ebi.ac.uk/pdbsum/1nmw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nmw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PIN1_HUMAN PIN1_HUMAN] Essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Displays a preference for an acidic residue N-terminal to the isomerized proline bond. Catalyzes pSer/Thr-Pro cis/trans isomerizations. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation.<ref>PMID:15664191</ref> <ref>PMID:16644721</ref> <ref>PMID:21497122</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/nm/1nmw_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=1nmw ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1NMW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NMW OCA].
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*[[Peptidyl-prolyl cis-trans isomerase 3D structures|Peptidyl-prolyl cis-trans isomerase 3D structures]]
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== References ==
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==Reference==
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<references/>
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Structural analysis of the mitotic regulator hPin1 in solution: insights into domain architecture and substrate binding., Bayer E, Goettsch S, Mueller JW, Griewel B, Guiberman E, Mayr LM, Bayer P, J Biol Chem. 2003 Jul 11;278(28):26183-93. Epub 2003 Apr 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12721297 12721297]
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Peptidylprolyl isomerase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Bayer E]]
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[[Category: Bayer, E.]]
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[[Category: Bayer P]]
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[[Category: Bayer, P.]]
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[[Category: Goettsch S]]
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[[Category: Goettsch, S.]]
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[[Category: Griewel B]]
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[[Category: Griewel, B.]]
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[[Category: Guiberman E]]
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[[Category: Guiberman, E.]]
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[[Category: Mayr L]]
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[[Category: Mayr, L.]]
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[[Category: Mueller JW]]
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[[Category: Mueller, J W.]]
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[[Category: SO4]]
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[[Category: a1/b1 loop]]
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[[Category: beta-alpha]]
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[[Category: ppiase domain]]
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[[Category: sulphate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:07:48 2008''
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Current revision

Solution structure of the PPIase domain of human Pin1

PDB ID 1nmw

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