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| | ==Study on structure and function relationships in human Pirin with Manganese ion== | | ==Study on structure and function relationships in human Pirin with Manganese ion== |
| - | <StructureSection load='4ewe' size='340' side='right' caption='[[4ewe]], [[Resolution|resolution]] 1.56Å' scene=''> | + | <StructureSection load='4ewe' size='340' side='right'caption='[[4ewe]], [[Resolution|resolution]] 1.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ewe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EWE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EWE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ewe]] 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=4EWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EWE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ero|4ero]], [[4ewa|4ewa]], [[4ewb|4ewb]], [[4ewd|4ewd]]</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=4ewe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ewe OCA], [https://pdbe.org/4ewe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ewe RCSB], [https://www.ebi.ac.uk/pdbsum/4ewe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ewe ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">human, PIR ([http://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'>[http://en.wikipedia.org/wiki/Quercetin_2,3-dioxygenase Quercetin 2,3-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.24 1.13.11.24] </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=4ewe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ewe OCA], [http://pdbe.org/4ewe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ewe RCSB], [http://www.ebi.ac.uk/pdbsum/4ewe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ewe ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PIR_HUMAN PIR_HUMAN]] Possible transcriptional coregulator. May contribute to the regulation of cellular processes via its interaction with BCL3. May be required for efficient terminal myeloid maturation of hematopoietic cells. May play a role in the regulation of cell migration. May promote apoptosis when overexpressed. Has quercetin 2,3-dioxygenase activity (in vitro).<ref>PMID:9079676</ref> <ref>PMID:17288615</ref> <ref>PMID:20010624</ref> <ref>PMID:20711196</ref> | + | [https://www.uniprot.org/uniprot/PIR_HUMAN PIR_HUMAN] Possible transcriptional coregulator. May contribute to the regulation of cellular processes via its interaction with BCL3. May be required for efficient terminal myeloid maturation of hematopoietic cells. May play a role in the regulation of cell migration. May promote apoptosis when overexpressed. Has quercetin 2,3-dioxygenase activity (in vitro).<ref>PMID:9079676</ref> <ref>PMID:17288615</ref> <ref>PMID:20010624</ref> <ref>PMID:20711196</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Quercetin 2,3-dioxygenase]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, L]] | + | [[Category: Chen L]] |
| - | [[Category: Esaka, S]] | + | [[Category: Esaka S]] |
| - | [[Category: Fu, R]] | + | [[Category: Fu R]] |
| - | [[Category: Liu, A]] | + | [[Category: Liu A]] |
| - | [[Category: Liu, F]] | + | [[Category: Liu F]] |
| - | [[Category: Rehmani, I]] | + | [[Category: Rehmani I]] |
| - | [[Category: Serrano, V]] | + | [[Category: Serrano V]] |
| - | [[Category: Beta sandwich]]
| + | |
| - | [[Category: Cupin]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Transcription cofactor activity]]
| + | |
| Structural highlights
Function
PIR_HUMAN Possible transcriptional coregulator. May contribute to the regulation of cellular processes via its interaction with BCL3. May be required for efficient terminal myeloid maturation of hematopoietic cells. May play a role in the regulation of cell migration. May promote apoptosis when overexpressed. Has quercetin 2,3-dioxygenase activity (in vitro).[1] [2] [3] [4]
Publication Abstract from PubMed
Pirin is a nuclear nonheme Fe protein of unknown function present in all human tissues. Here we describe that pirin may act as a redox sensor for the nuclear factor kappaB (NF-kappaB) transcription factor, a critical mediator of intracellular signaling that has been linked to cellular responses to proinflammatory signals and controls the expression of a vast array of genes involved in immune and stress responses. Pirin's regulatory effect was tested with several metals and at different oxidations states, and our spectroscopic results show that only the ferric form of pirin substantially facilitates binding of NF-kappaB proteins to target kappaB genes, a finding that suggests that pirin performs a redox-sensing role in NF-kappaB regulation. The molecular mechanism of such a metal identity- and redox state-dependent regulation is revealed by our structural studies of pirin. The ferrous and ferric pirin proteins differ only by one electron, yet they have distinct conformations. The Fe center is shown to play an allosteric role on an R-shaped surface area that has two distinct conformations based on the identity and the formal redox state of the metal. We show that the R-shaped area composes the interface for pirin-NF-kappaB binding that is responsible for modulation of NF-kappaB's DNA-binding properties. The nonheme Fe protein pirin is proposed to serve as a reversible functional switch that enables NF-kappaB to respond to changes in the redox levels of the cell nucleus.
Pirin is an iron-dependent redox regulator of NF-kappaB.,Liu F, Rehmani I, Esaki S, Fu R, Chen L, de Serrano V, Liu A Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9722-7. doi:, 10.1073/pnas.1221743110. Epub 2013 May 28. PMID:23716661[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wendler WM, Kremmer E, Forster R, Winnacker EL. Identification of pirin, a novel highly conserved nuclear protein. J Biol Chem. 1997 Mar 28;272(13):8482-9. PMID:9079676
- ↑ Gelbman BD, Heguy A, O'Connor TP, Zabner J, Crystal RG. Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis. Respir Res. 2007 Feb 8;8:10. PMID:17288615 doi:http://dx.doi.org/10.1186/1465-9921-8-10
- ↑ Licciulli S, Cambiaghi V, Scafetta G, Gruszka AM, Alcalay M. Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation. Leukemia. 2010 Feb;24(2):429-37. doi: 10.1038/leu.2009.247. Epub 2009 Dec 10. PMID:20010624 doi:http://dx.doi.org/10.1038/leu.2009.247
- ↑ Miyazaki I, Simizu S, Okumura H, Takagi S, Osada H. A small-molecule inhibitor shows that pirin regulates migration of melanoma cells. Nat Chem Biol. 2010 Sep;6(9):667-73. Epub 2010 Aug 15. PMID:20711196 doi:10.1038/nchembio.423
- ↑ Liu F, Rehmani I, Esaki S, Fu R, Chen L, de Serrano V, Liu A. Pirin is an iron-dependent redox regulator of NF-kappaB. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9722-7. doi:, 10.1073/pnas.1221743110. Epub 2013 May 28. PMID:23716661 doi:10.1073/pnas.1221743110
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