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| | ==Structure of actinomycin D d(ATGCGGCAT) complex== | | ==Structure of actinomycin D d(ATGCGGCAT) complex== |
| - | <StructureSection load='4hiv' size='340' side='right' caption='[[4hiv]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='4hiv' size='340' side='right'caption='[[4hiv]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hiv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_antibioticus Streptomyces antibioticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HIV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HIV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hiv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_antibioticus Streptomyces antibioticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HIV FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DVA:D-VALINE'>DVA</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=PXZ:2-AMINO-1,9-DICARBONYL-4,6-DIMETHYL-10-DEHYDRO-PHENOXAZIN-3-ONE'>PXZ</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</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]] 2.6Å</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=4hiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hiv OCA], [http://pdbe.org/4hiv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hiv RCSB], [http://www.ebi.ac.uk/pdbsum/4hiv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hiv ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DVA:D-VALINE'>DVA</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=PXZ:2-AMINO-1,9-DICARBONYL-4,6-DIMETHYL-10-DEHYDRO-PHENOXAZIN-3-ONE'>PXZ</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</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=4hiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hiv OCA], [https://pdbe.org/4hiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hiv RCSB], [https://www.ebi.ac.uk/pdbsum/4hiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hiv 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 antibioticus]] | | [[Category: Streptomyces antibioticus]] |
| - | [[Category: Hou, M H]] | + | [[Category: Hou MH]] |
| - | [[Category: Lo, Y S]] | + | [[Category: Lo YS]] |
| - | [[Category: Tseng, W H]] | + | [[Category: Tseng WH]] |
| - | [[Category: Cgg tripleat repeat]]
| + | |
| - | [[Category: Dna-antibiotic complex]]
| + | |
| - | [[Category: Double helix dna]]
| + | |
| - | [[Category: Left-handed twist]]
| + | |
| - | [[Category: Neurological disease]]
| + | |
| - | [[Category: Nucleotide flipping-out]]
| + | |
| - | [[Category: Sharp kink]]
| + | |
| Structural highlights
Publication Abstract from PubMed
The potent anticancer drug actinomycin D (ActD) functions by intercalating into DNA at GpC sites, thereby interrupting essential biological processes including replication and transcription. Certain neurological diseases are correlated with the expansion of (CGG)n trinucleotide sequences, which contain many contiguous GpC sites separated by a single G:G mispair. To characterize the binding of ActD to CGG triplet repeat sequences, the structural basis for the strong binding of ActD to neighbouring GpC sites flanking a G:G mismatch has been determined based on the crystal structure of ActD bound to ATGCGGCAT, which contains a CGG triplet sequence. The binding of ActD molecules to GCGGC causes many unexpected conformational changes including nucleotide flipping out, a sharp bend and a left-handed twist in the DNA helix via a two site-binding model. Heat denaturation, circular dichroism and surface plasmon resonance analyses showed that adjacent GpC sequences flanking a G:G mismatch are preferred ActD-binding sites. In addition, ActD was shown to bind the hairpin conformation of (CGG)16 in a pairwise combination and with greater stability than that of other DNA intercalators. Our results provide evidence of a possible biological consequence of ActD binding to CGG triplet repeat sequences.
The structural basis of actinomycin D-binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats.,Lo YS, Tseng WH, Chuang CY, Hou MH Nucleic Acids Res. 2013 Apr 1;41(7):4284-94. doi: 10.1093/nar/gkt084. Epub 2013, Feb 13. PMID:23408860[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lo YS, Tseng WH, Chuang CY, Hou MH. The structural basis of actinomycin D-binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats. Nucleic Acids Res. 2013 Apr 1;41(7):4284-94. doi: 10.1093/nar/gkt084. Epub 2013, Feb 13. PMID:23408860 doi:10.1093/nar/gkt084
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