5wc9
From Proteopedia
(Difference between revisions)
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<StructureSection load='5wc9' size='340' side='right' caption='[[5wc9]], [[Resolution|resolution]] 3.15Å' scene=''> | <StructureSection load='5wc9' size='340' side='right' caption='[[5wc9]], [[Resolution|resolution]] 3.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5wc9]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WC9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wc9]] is a 8 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=5WC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WC9 FirstGlance]. <br> |
| - | </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=5wc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wc9 OCA], [http://pdbe.org/5wc9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wc9 RCSB], [http://www.ebi.ac.uk/pdbsum/5wc9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wc9 ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POU1F1, GHF1, PIT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5wc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wc9 OCA], [http://pdbe.org/5wc9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wc9 RCSB], [http://www.ebi.ac.uk/pdbsum/5wc9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wc9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PIT1_HUMAN PIT1_HUMAN]] Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5'-TAAAT-3'. Activates growth hormone and prolactin genes (PubMed:22010633, PubMed:26612202).<ref>PMID:22010633</ref> <ref>PMID:26612202</ref> | [[http://www.uniprot.org/uniprot/PIT1_HUMAN PIT1_HUMAN]] Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5'-TAAAT-3'. Activates growth hormone and prolactin genes (PubMed:22010633, PubMed:26612202).<ref>PMID:22010633</ref> <ref>PMID:26612202</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Overexpression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) is linked to a number of autoimmune diseases and cancer. MIF production has been correlated to the number of CATT repeats in a microsatellite region upstream of the MIF gene. We have characterized the interaction of pituitary-specific positive transcription factor 1 (Pit-1) with a portion of the MIF promoter region flanking a microsatellite polymorphism (-794 CATT5-8). Using fluorescence anisotropy, we quantified tight complex formation between Pit-1 and an oligonucleotide consisting of eight consecutive CATT repeats (8xCATT) with an apparent Kd of 35 nM. Using competition experiments we found a 23 base pair oligonucleotide with 4xCATT repeats to be the minimum DNA sequence necessary for high affinity interaction with Pit-1. The stoichiometry of the Pit-1 DNA interaction was determined to be 2:1 and binding is cooperative in nature. We subsequently structurally characterized the complex and discovered a completely novel binding mode for Pit-1 in contrast to previously described Pit-1 complex structures. The affinity of Pit-1 for the CATT target sequence was found to be highly dependent on cooperativity. This work lays the groundwork for understanding transcriptional regulation of MIF and pursuing Pit-1 as a therapeutic target to treat MIF-mediated inflammatory disorders. | ||
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| + | Biochemical and structural characterization of a novel cooperative binding mode by Pit-1 with CATT repeats in the macrophage migration inhibitory factor promoter.,Agarwal S, Cho TY Nucleic Acids Res. 2017 Nov 23. pii: 4653535. doi: 10.1093/nar/gkx1183. PMID:29186613<ref>PMID:29186613</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5wc9" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Agarwal, S]] | [[Category: Agarwal, S]] | ||
[[Category: Cho, T Y]] | [[Category: Cho, T Y]] | ||
Revision as of 07:34, 13 December 2017
Human Pit-1 and 4xCATT DNA complex
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