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| | ==Crystal structure of echinomycin-d(ACGACGT/ACGTCGT) complex== | | ==Crystal structure of echinomycin-d(ACGACGT/ACGTCGT) complex== |
| - | <StructureSection load='5yty' size='340' side='right' caption='[[5yty]], [[Resolution|resolution]] 1.58Å' scene=''> | + | <StructureSection load='5yty' size='340' side='right'caption='[[5yty]], [[Resolution|resolution]] 1.58Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5yty]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_echinatus Streptomyces echinatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YTY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yty]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_echinatus Streptomyces echinatus] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YTY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=QUI:2-CARBOXYQUINOXALINE'>QUI</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.58Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=N2C:N,S-DIMETHYLCYSTEINE'>N2C</scene>, <scene name='pdbligand=NCY:N-METHYLCYSTEINE'>NCY</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=N2C:N,S-DIMETHYLCYSTEINE'>N2C</scene>, <scene name='pdbligand=NCY:N-METHYLCYSTEINE'>NCY</scene>, <scene name='pdbligand=QUI:2-CARBOXYQUINOXALINE'>QUI</scene></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=5yty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yty OCA], [http://pdbe.org/5yty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yty RCSB], [http://www.ebi.ac.uk/pdbsum/5yty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yty 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=5yty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yty OCA], [https://pdbe.org/5yty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yty RCSB], [https://www.ebi.ac.uk/pdbsum/5yty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yty ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Streptomyces echinatus]] | | [[Category: Streptomyces echinatus]] |
| - | [[Category: Hou, M H]] | + | [[Category: Unidentified]] |
| - | [[Category: Kao, Y F]] | + | [[Category: Hou MH]] |
| - | [[Category: Wu, P C]] | + | [[Category: Kao YF]] |
| - | [[Category: Antibiotic-dna complex]] | + | [[Category: Wu PC]] |
| - | [[Category: Dna intercalator]]
| + | |
| - | [[Category: Echinomycin-dna complex]]
| + | |
| - | [[Category: Heptamer duplex]]
| + | |
| - | [[Category: Watson-crick]]
| + | |
| Structural highlights
5yty is a 4 chain structure with sequence from Streptomyces echinatus and Unidentified. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.58Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
Small-molecule compounds that target mismatched base pairs in DNA offer a novel prospective for cancer diagnosis and therapy. The potent anticancer antibiotic echinomycin functions by intercalating into DNA at CpG sites. Surprisingly, we found that the drug strongly prefers to bind to consecutive CpG steps separated by a single T:T mismatch. The preference appears to result from enhanced cooperativity associated with the binding of the second echinomycin molecule. Crystallographic studies reveal that this preference originates from the staggered quinoxaline rings of the two neighboring antibiotic molecules that surround the T:T mismatch forming continuous stacking interactions within the duplex. These and other associated changes in DNA conformation allow the formation of a minor groove pocket for tight binding of the second echinomycin molecule. We also show that echinomycin displays enhanced cytotoxicity against mismatch repair-deficient cell lines, raising the possibility of repurposing the drug for detection and treatment of mismatch repair-deficient cancers.
Cooperative recognition of T:T mismatch by echinomycin causes structural distortions in DNA duplex.,Wu PC, Tzeng SL, Chang CK, Kao YF, Waring MJ, Hou MH Nucleic Acids Res. 2018 May 8. pii: 4993785. doi: 10.1093/nar/gky345. PMID:29741655[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu PC, Tzeng SL, Chang CK, Kao YF, Waring MJ, Hou MH. Cooperative recognition of T:T mismatch by echinomycin causes structural distortions in DNA duplex. Nucleic Acids Res. 2018 May 8. pii: 4993785. doi: 10.1093/nar/gky345. PMID:29741655 doi:http://dx.doi.org/10.1093/nar/gky345
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