4u85: Difference between revisions

Revision as of 01:19, 19 January 2017

Human Pin1 with cysteine sulfinic acid 113

Structural highlights

4u85 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	15P
NonStd Res:	CSD
Related:	4u84, 4u86
Activity:	Peptidylprolyl isomerase, with EC number 5.2.1.8
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

The unique proline isomerase Pin1 is pivotal for protecting against age-dependent neurodegeneration in Alzheimer's disease (AD), with its inhibition providing a molecular link between tangle and plaque pathologies. Pin1 is oxidatively modified in human AD brains, but little is known about its regulatory mechanisms and pathological significance of such Pin1 modification. In this paper, our determination of crystal structures of oxidized Pin1 reveals a series of Pin1 oxidative modifications on Cys113 in a sequential fashion. Cys113 oxidization is further confirmed by generating antibodies specifically recognizing oxidized Cys113 of Pin1. Furthermore, Pin1 oxidation on Cys113 inactivates its catalytic activity in vitro, and Ala point substitution of Cys113 inactivates the ability of Pin1 to isomerize tau as well as to promote protein turnover of tau and APP. Moreover, redox regulation affects Pin1 subcellular localization and Pin1-mediated neuronal survival in response to hypoxia treatment. Importantly, Cys113-oxidized Pin1 is significantly increased in human AD brain comparing to age-matched controls. These results not only identify a novel Pin1 oxidation site to be the critical catalytic residue Cys113, but also provide a novel oxidative regulation mechanism for inhibiting Pin1 activity in AD. These results suggest that preventing Pin1 oxidization might help to reduce the risk of AD.

Pin1 cysteine-113 oxidation inhibits its catalytic activity and cellular function in Alzheimer's disease.,Chen CH, Li W, Sultana R, You MH, Kondo A, Shahpasand K, Kim BM, Luo ML, Nechama M, Lin YM, Yao Y, Lee TH, Zhou XZ, Swomley AM, Allan Butterfield D, Zhang Y, Lu KP Neurobiol Dis. 2015 Apr;76:13-23. doi: 10.1016/j.nbd.2014.12.027. Epub 2015 Jan, 6. PMID:25576397^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Chen CH, Li W, Sultana R, You MH, Kondo A, Shahpasand K, Kim BM, Luo ML, Nechama M, Lin YM, Yao Y, Lee TH, Zhou XZ, Swomley AM, Allan Butterfield D, Zhang Y, Lu KP. Pin1 cysteine-113 oxidation inhibits its catalytic activity and cellular function in Alzheimer's disease. Neurobiol Dis. 2015 Apr;76:13-23. doi: 10.1016/j.nbd.2014.12.027. Epub 2015 Jan, 6. PMID:25576397 doi:https://dx.doi.org/10.1016/j.nbd.2014.12.027

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OCA

[1] 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

[2] 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

[3] 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

[4] Chen CH, Li W, Sultana R, You MH, Kondo A, Shahpasand K, Kim BM, Luo ML, Nechama M, Lin YM, Yao Y, Lee TH, Zhou XZ, Swomley AM, Allan Butterfield D, Zhang Y, Lu KP. Pin1 cysteine-113 oxidation inhibits its catalytic activity and cellular function in Alzheimer's disease. Neurobiol Dis. 2015 Apr;76:13-23. doi: 10.1016/j.nbd.2014.12.027. Epub 2015 Jan, 6. PMID:25576397 doi:https://dx.doi.org/10.1016/j.nbd.2014.12.027

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@@ Line 1: / Line 1: @@
 ==Human Pin1 with cysteine sulfinic acid 113==
 <StructureSection load='4u85' size='340' side='right' caption='[[4u85]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u84|4u84]], [[4u86|4u86]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u85 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u85 RCSB], [http://www.ebi.ac.uk/pdbsum/4u85 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u85 OCA], [http://pdbe.org/4u85 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u85 RCSB], [http://www.ebi.ac.uk/pdbsum/4u85 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u85 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4u85" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Peptidyl-prolyl cis-trans isomerase|Peptidyl-prolyl cis-trans isomerase]]
 == References ==
 <references/>

4u85: Difference between revisions

Revision as of 01:19, 19 January 2017

Human Pin1 with cysteine sulfinic acid 113

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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