2kbu: Difference between revisions
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< | ==NMR solution structure of Pin1 WW domain mutant with beta turn mimic at position 12== | ||
<StructureSection load='2kbu' size='340' side='right'caption='[[2kbu]]' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2kbu]] 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=2KBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KBU FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 15 models</td></tr> | ||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CFD:(2R,3E,5R)-5-AMINO-2,4-DIMETHYLHEX-3-ENAL'>CFD</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=2kbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kbu OCA], [https://pdbe.org/2kbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kbu RCSB], [https://www.ebi.ac.uk/pdbsum/2kbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kbu ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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> | |||
== 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/kb/2kbu_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2kbu ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
beta-Turns are common conformations that enable proteins to adopt globular structures, and their formation is often rate limiting for folding. beta-Turn mimics, molecules that replace the i + 1 and i + 2 amino acid residues of a beta-turn, are envisioned to act as folding nucleators by preorganizing the pendant polypeptide chains, thereby lowering the activation barrier for beta-sheet formation. However, the crucial kinetic experiments to demonstrate that beta-turn mimics can act as strong nucleators in the context of a cooperatively folding protein have not been reported. We have incorporated 6 beta-turn mimics simulating varied beta-turn types in place of 2 residues in an engineered beta-turn 1 or beta-bulge turn 1 of the Pin 1 WW domain, a three-stranded beta-sheet protein. We present 2 lines of kinetic evidence that the inclusion of beta-turn mimics alters beta-sheet folding rates, enabling us to classify beta-turn mimics into 3 categories: those that are weak nucleators but permit Pin WW folding, native-like nucleators, and strong nucleators. Strong nucleators accelerate folding relative to WW domains incorporating all alpha-amino acid sequences. A solution NMR structure reveals that the native Pin WW beta-sheet structure is retained upon incorporating a strong E-olefin nucleator. These beta-turn mimics can now be used to interrogate protein folding transition state structures and the 2 kinetic analyses presented can be used to assess the nucleation capacity of other beta-turn mimics. | |||
Evaluating {beta}-turn mimics as {beta}-sheet folding nucleators.,Fuller AA, Du D, Liu F, Davoren JE, Bhabha G, Kroon G, Case DA, Dyson HJ, Powers ET, Wipf P, Gruebele M, Kelly JW Proc Natl Acad Sci U S A. 2009 Jun 18. PMID:19541614<ref>PMID:19541614</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2kbu" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Peptidyl-prolyl cis-trans isomerase 3D structures|Peptidyl-prolyl cis-trans isomerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: Bhabha G]] | |||
== | [[Category: Case DA]] | ||
< | [[Category: Fuller AA]] | ||
[[Category: | |||
[[Category: | |||
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Latest revision as of 12:14, 6 November 2024
NMR solution structure of Pin1 WW domain mutant with beta turn mimic at position 12NMR solution structure of Pin1 WW domain mutant with beta turn mimic at position 12
Structural highlights
FunctionPIN1_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.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedbeta-Turns are common conformations that enable proteins to adopt globular structures, and their formation is often rate limiting for folding. beta-Turn mimics, molecules that replace the i + 1 and i + 2 amino acid residues of a beta-turn, are envisioned to act as folding nucleators by preorganizing the pendant polypeptide chains, thereby lowering the activation barrier for beta-sheet formation. However, the crucial kinetic experiments to demonstrate that beta-turn mimics can act as strong nucleators in the context of a cooperatively folding protein have not been reported. We have incorporated 6 beta-turn mimics simulating varied beta-turn types in place of 2 residues in an engineered beta-turn 1 or beta-bulge turn 1 of the Pin 1 WW domain, a three-stranded beta-sheet protein. We present 2 lines of kinetic evidence that the inclusion of beta-turn mimics alters beta-sheet folding rates, enabling us to classify beta-turn mimics into 3 categories: those that are weak nucleators but permit Pin WW folding, native-like nucleators, and strong nucleators. Strong nucleators accelerate folding relative to WW domains incorporating all alpha-amino acid sequences. A solution NMR structure reveals that the native Pin WW beta-sheet structure is retained upon incorporating a strong E-olefin nucleator. These beta-turn mimics can now be used to interrogate protein folding transition state structures and the 2 kinetic analyses presented can be used to assess the nucleation capacity of other beta-turn mimics. Evaluating {beta}-turn mimics as {beta}-sheet folding nucleators.,Fuller AA, Du D, Liu F, Davoren JE, Bhabha G, Kroon G, Case DA, Dyson HJ, Powers ET, Wipf P, Gruebele M, Kelly JW Proc Natl Acad Sci U S A. 2009 Jun 18. PMID:19541614[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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