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| | ==Crystal structure of the Pdx1 homeodomain in complex with DNA== | | ==Crystal structure of the Pdx1 homeodomain in complex with DNA== |
| - | <StructureSection load='2h1k' size='340' side='right' caption='[[2h1k]], [[Resolution|resolution]] 2.42Å' scene=''> | + | <StructureSection load='2h1k' size='340' side='right'caption='[[2h1k]], [[Resolution|resolution]] 2.42Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2h1k]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Golden_hamster Golden hamster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H1K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2H1K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2h1k]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Golden_hamster Golden hamster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H1K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H1K FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IPF1, PDX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10036 Golden hamster])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IPF1, PDX1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10036 Golden hamster])</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=2h1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h1k OCA], [http://pdbe.org/2h1k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2h1k RCSB], [http://www.ebi.ac.uk/pdbsum/2h1k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2h1k 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=2h1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h1k OCA], [https://pdbe.org/2h1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h1k RCSB], [https://www.ebi.ac.uk/pdbsum/2h1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h1k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDX1_MESAU PDX1_MESAU]] Activates insulin and somatostatin gene transcription. Key regulator of islet peptide hormone expression but also responsible for the development of the pancreas, most probably by determining maturation and differentiation of common pancreatic precursor cells in the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3' (By similarity). | + | [[https://www.uniprot.org/uniprot/PDX1_MESAU PDX1_MESAU]] Activates insulin and somatostatin gene transcription. Key regulator of islet peptide hormone expression but also responsible for the development of the pancreas, most probably by determining maturation and differentiation of common pancreatic precursor cells in the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3' (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Golden hamster]] | | [[Category: Golden hamster]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Guanga, G P]] | | [[Category: Guanga, G P]] |
| | [[Category: Longo, A]] | | [[Category: Longo, A]] |
| Structural highlights
Function
[PDX1_MESAU] Activates insulin and somatostatin gene transcription. Key regulator of islet peptide hormone expression but also responsible for the development of the pancreas, most probably by determining maturation and differentiation of common pancreatic precursor cells in the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3' (By similarity).
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
Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription factor belonging to the ParaHox family. Pdx1 plays an essential role in pancreatic endocrine and exocrine cell development and maintenance of adult islet beta-cell function. Mutations in the human pdx1 gene are linked to an early onset form of non-insulin-dependent diabetes mellitus, MODY-4. We demonstrate that the homeodomain reproduces the binding specificity of the full-length protein. We report the 2.4 A resolution crystal structure of the homeodomain bound to a target DNA. The two Pdx1/DNA complexes in the asymmetric unit display conformational differences: in the DNA curvature, the orientation of the homeodomain in the major groove, and the order of the N-terminal arm. Comparing the two complexes indicates invariant protein-DNA contacts, and variant contacts that are unique to each binding orientation. An induced fit model is proposed that depends on the DNA conformation and provides a mechanism for nonlocal contributions to binding specificity.
Structural basis for induced fit mechanisms in DNA recognition by the Pdx1 homeodomain.,Longo A, Guanga GP, Rose RB Biochemistry. 2007 Mar 20;46(11):2948-57. Epub 2007 Feb 23. PMID:17315980[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Longo A, Guanga GP, Rose RB. Structural basis for induced fit mechanisms in DNA recognition by the Pdx1 homeodomain. Biochemistry. 2007 Mar 20;46(11):2948-57. Epub 2007 Feb 23. PMID:17315980 doi:10.1021/bi060969l
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