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| [[Image:2a5r.gif|left|200px]]
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| {{Structure
| | ==Complex of tetra-(4-n-methylpyridyl) porphin with monomeric parallel-stranded DNA tetraplex, snap-back 3+1 3' G-tetrad, single-residue chain reversal loops, GAG triad in the context of GAAG diagonal loop, C-MYC promoter, NMR, 6 struct.== |
| |PDB= 2a5r |SIZE=350|CAPTION= <scene name='initialview01'>2a5r</scene>
| | <StructureSection load='2a5r' size='340' side='right'caption='[[2a5r]]' scene=''> |
| |SITE=
| | == Structural highlights == |
| |LIGAND= <scene name='pdbligand=POH:5,10,15,20-TETRA-(4-N-METHYLPYRIDYL) PORPHINE'>POH</scene>
| | <table><tr><td colspan='2'>[[2a5r]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A5R FirstGlance]. <br> |
| |ACTIVITY=
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| |GENE=
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=POH:(1Z,4Z,9Z,15Z)-5,10,15,20-TETRAKIS(1-METHYLPYRIDIN-1-IUM-4-YL)-21,23-DIHYDROPORPHYRIN'>POH</scene></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=2a5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a5r OCA], [https://pdbe.org/2a5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a5r RCSB], [https://www.ebi.ac.uk/pdbsum/2a5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a5r ProSAT]</span></td></tr> |
| | | </table> |
| '''Complex of tetra-(4-n-methylpyridyl) porphin with monomeric parallel-stranded DNA tetraplex, snap-back 3+1 3' G-tetrad, single-residue chain reversal loops, GAG triad in the context of GAAG diagonal loop, C-MYC promoter, NMR, 6 struct.'''
| | __TOC__ |
| | | </StructureSection> |
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| ==Overview== | |
| It has been widely accepted that DNA can adopt other biologically relevant structures beside the Watson-Crick double helix. One recent important example is the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in the MYC (or c-myc) promoter region, which regulates the transcription of the MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the first structure of a DNA fragment containing five guanine tracts from this region. An unusual G-quadruplex fold, which was derived from NMR restraints using unambiguous model-independent resonance assignment approaches, involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3'-end syn guanine. We have determined the structure of the complex formed between this G-quadruplex and TMPyP4. This structural information, combined with details of small-molecule interaction, provides a platform for the design of anticancer drugs targeting multi-guanine-tract sequences that are found in the MYC and other oncogenic promoters, as well as in telomeres.
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| ==About this Structure== | |
| 2A5R is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A5R OCA].
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| ==Reference== | |
| Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter., Phan AT, Kuryavyi V, Gaw HY, Patel DJ, Nat Chem Biol. 2005 Aug;1(3):167-73. Epub 2005 Jul 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16408022 16408022]
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| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Protein complex]] | | [[Category: Large Structures]] |
| [[Category: Gaw, H Y.]] | | [[Category: Gaw HY]] |
| [[Category: Kuryavyi, V V.]] | | [[Category: Kuryavyi VV]] |
| [[Category: Patel, D J.]] | | [[Category: Patel DJ]] |
| [[Category: Phan, A T.]] | | [[Category: Phan AT]] |
| [[Category: POH]]
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| [[Category: monomeric parallel-stranded quadruplex; c-myc promoter 3+1 g-tetrad; single nucleotide chain reversal loop; gag triad; gaag loop]]
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| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:45:41 2008''
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