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| | <StructureSection load='1zcn' size='340' side='right'caption='[[1zcn]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1zcn' size='340' side='right'caption='[[1zcn]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zcn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZCN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zcn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZCN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pin|1pin]], [[1f8a|1f8a]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIN1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <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'>[https://proteopedia.org/fgij/fg.htm?mol=1zcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zcn OCA], [https://pdbe.org/1zcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zcn RCSB], [https://www.ebi.ac.uk/pdbsum/1zcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zcn ProSAT]</span></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=1zcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zcn OCA], [https://pdbe.org/1zcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zcn RCSB], [https://www.ebi.ac.uk/pdbsum/1zcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zcn 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>
| + | [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]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peptidylprolyl isomerase]]
| + | [[Category: Bowman ME]] |
| - | [[Category: Bowman, M E]] | + | [[Category: Dendel G]] |
| - | [[Category: Dendel, G]] | + | [[Category: Gruebele M]] |
| - | [[Category: Gruebele, M]] | + | [[Category: Jager M]] |
| - | [[Category: Jager, M]] | + | [[Category: Kelly JW]] |
| - | [[Category: Kelly, J W]] | + | [[Category: Nguyen H]] |
| - | [[Category: Nguyen, H]] | + | [[Category: Noel JP]] |
| - | [[Category: Noel, J P]] | + | [[Category: Zhang Y]] |
| - | [[Category: Zhang, Y]] | + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Type i beta-turn]]
| + | |
| - | [[Category: Ww domain]]
| + | |
| 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 PubMed
Protein folding barriers result from a combination of factors including unavoidable energetic frustration from nonnative interactions, natural variation and selection of the amino acid sequence for function, and/or selection pressure against aggregation. The rate-limiting step for human Pin1 WW domain folding is the formation of the loop 1 substructure. The native conformation of this six-residue loop positions side chains that are important for mediating protein-protein interactions through the binding of Pro-rich sequences. Replacement of the wild-type loop 1 primary structure by shorter sequences with a high propensity to fold into a type-I' beta-turn conformation or the statistically preferred type-I G1 bulge conformation accelerates WW domain folding by almost an order of magnitude and increases thermodynamic stability. However, loop engineering to optimize folding energetics has a significant downside: it effectively eliminates WW domain function according to ligand-binding studies. The energetic contribution of loop 1 to ligand binding appears to have evolved at the expense of fast folding and additional protein stability. Thus, the two-state barrier exhibited by the wild-type human Pin1 WW domain principally results from functional requirements, rather than from physical constraints inherent to even the most efficient loop formation process.
Structure-function-folding relationship in a WW domain.,Jager M, Zhang Y, Bieschke J, Nguyen H, Dendle M, Bowman ME, Noel JP, Gruebele M, Kelly JW Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10648-53. Epub 2006 Jun 28. PMID:16807295[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dougherty MK, Muller J, Ritt DA, Zhou M, Zhou XZ, Copeland TD, Conrads TP, Veenstra TD, Lu KP, Morrison DK. Regulation of Raf-1 by direct feedback phosphorylation. Mol Cell. 2005 Jan 21;17(2):215-24. PMID:15664191 doi:10.1016/j.molcel.2004.11.055
- ↑ Yu L, Mohamed AJ, Vargas L, Berglof A, Finn G, Lu KP, Smith CI. Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1. J Biol Chem. 2006 Jun 30;281(26):18201-7. Epub 2006 Apr 27. PMID:16644721 doi:10.1074/jbc.M603090200
- ↑ Lee TH, Chen CH, Suizu F, Huang P, Schiene-Fischer C, Daum S, Zhang YJ, Goate A, Chen RH, Zhou XZ, Lu KP. Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. Mol Cell. 2011 Apr 22;42(2):147-59. doi: 10.1016/j.molcel.2011.03.005. Epub 2011 , Apr 14. PMID:21497122 doi:10.1016/j.molcel.2011.03.005
- ↑ Jager M, Zhang Y, Bieschke J, Nguyen H, Dendle M, Bowman ME, Noel JP, Gruebele M, Kelly JW. Structure-function-folding relationship in a WW domain. Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10648-53. Epub 2006 Jun 28. PMID:16807295
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