| 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]
Publication Abstract from PubMed
Crown ethers are small, cyclic polyethers that have found wide-spread use in phase-transfer catalysis and, to a certain degree, in protein chemistry. Crown ethers readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6. We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols. Our studies show that crown ethers can modify protein surface behavior dramatically by stabilizing either intra- or intermolecular interactions. Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain-domain interactions, stabilization in organic solvents, and crystallization.
Crowning Proteins: Modulating the Protein Surface Properties using Crown Ethers.,Lee CC, Maestre-Reyna M, Hsu KC, Wang HC, Liu CI, Jeng WY, Lin LL, Wood R, Chou CC, Yang JM, Wang AH Angew Chem Int Ed Engl. 2014 Oct 6. doi: 10.1002/anie.201405664. PMID:25287606[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
- ↑ Lee CC, Maestre-Reyna M, Hsu KC, Wang HC, Liu CI, Jeng WY, Lin LL, Wood R, Chou CC, Yang JM, Wang AH. Crowning Proteins: Modulating the Protein Surface Properties using Crown Ethers. Angew Chem Int Ed Engl. 2014 Oct 6. doi: 10.1002/anie.201405664. PMID:25287606 doi:http://dx.doi.org/10.1002/anie.201405664
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