2lkx

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==NMR structure of the homeodomain of Pitx2 in complex with a TAATCC DNA binding site==
==NMR structure of the homeodomain of Pitx2 in complex with a TAATCC DNA binding site==
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<StructureSection load='2lkx' size='340' side='right' caption='[[2lkx]], [[NMR_Ensembles_of_Models | 17 NMR models]]' scene=''>
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<StructureSection load='2lkx' size='340' side='right'caption='[[2lkx]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2lkx]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1yz8 1yz8]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LKX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LKX FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2lkx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1yz8 1yz8]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LKX FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PITX3, PTX3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<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=2lkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lkx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lkx RCSB], [http://www.ebi.ac.uk/pdbsum/2lkx PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lkx OCA], [https://pdbe.org/2lkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lkx RCSB], [https://www.ebi.ac.uk/pdbsum/2lkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lkx ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Disease ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/PITX2_HUMAN PITX2_HUMAN] Peters anomaly;Axenfeld anomaly;Rieger anomaly;Ring dermoid of cornea;Axenfeld-Rieger syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
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We have determined the solution structure of a complex containing the K50 class homeodomain Pituitary homeobox protein 2 (PITX2) bound to its consensus DNA site (TAATCC). Previous studies have suggested that residue 50 is an important determinant of differential DNA-binding specificity among homeodomains. Although structures of several homeodomain-DNA complexes have been determined, this is the first structure of a native K50 class homeodomain. The only K50 homeodomain structure determined previously is an X-ray crystal structure of an altered specificity mutant, Engrailed Q50K (EnQ50K). Analysis of the NMR structure of the PITX2 homeodomain indicates that the lysine at position 50 makes contacts with two guanines on the antisense strand of the DNA, adjacent to the TAAT core DNA sequence, consistent with the structure of EnQ50K. Our evidence suggests that this side chain may make fluctuating interactions with the DNA, which is complementary to the crystal data for EnQ50K. There are differences in the tertiary structure between the native K50 structure and that of EnQ50K, which may explain differences in affinity and specificity between these proteins. Mutations in the human PITX2 gene are responsible for Rieger syndrome, an autosomal dominant disorder. Analysis of the residues mutated in Rieger syndrome indicates that many of these residues are involved in DNA binding, while others are involved in formation of the hydrophobic core of the protein. Overall, the role of K50 in homeodomain recognition is further clarified, and the results indicate that native K50 homeodomains may exhibit differences from altered specificity mutants.
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== Function ==
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[https://www.uniprot.org/uniprot/PITX2_HUMAN PITX2_HUMAN] Controls cell proliferation in a tissue-specific manner and is involved in morphogenesis. During embryonic development, exerts a role in the expansion of muscle progenitors. May play a role in the proper localization of asymmetric organs such as the heart and stomach. Isoform PTX2C is involved in left-right asymmetry the developing embryo (By similarity).
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Solution structure of the K50 class homeodomain PITX2 bound to DNA and implications for mutations that cause Rieger syndrome.,Chaney BA, Clark-Baldwin K, Dave V, Ma J, Rance M Biochemistry. 2005 May 24;44(20):7497-511. PMID:15895993<ref>PMID:15895993</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Baird-Titus, J M]]
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[[Category: Large Structures]]
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[[Category: Chaney, B A]]
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[[Category: Baird-Titus JM]]
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[[Category: Clark-Baldwin, K]]
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[[Category: Chaney BA]]
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[[Category: Dave, V]]
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[[Category: Clark-Baldwin K]]
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[[Category: Doerdelmann, T]]
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[[Category: Dave V]]
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[[Category: Ma, J]]
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[[Category: Doerdelmann T]]
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[[Category: Transcription-dna complex]]
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[[Category: Ma J]]

Current revision

NMR structure of the homeodomain of Pitx2 in complex with a TAATCC DNA binding site

PDB ID 2lkx

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