2kbu: Difference between revisions
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<StructureSection load='2kbu' size='340' side='right'caption='[[2kbu]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | <StructureSection load='2kbu' size='340' side='right'caption='[[2kbu]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2kbu]] is a 1 chain structure. 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 [ | <table><tr><td colspan='2'>[[2kbu]] is a 1 chain structure. 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> | ||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CFD:(2R,3E,5R)-5-AMINO-2,4-DIMETHYLHEX-3-ENAL'>CFD</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CFD:(2R,3E,5R)-5-AMINO-2,4-DIMETHYLHEX-3-ENAL'>CFD</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <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> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Revision as of 21:03, 20 October 2021
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
Function[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.[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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