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| | <StructureSection load='1mnv' size='340' side='right'caption='[[1mnv]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='1mnv' size='340' side='right'caption='[[1mnv]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1mnv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_antibioticus"_waksman_and_woodruff_1941 "actinomyces antibioticus" waksman and woodruff 1941]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MNV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1mnv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptomyces_antibioticus Streptomyces antibioticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MNV 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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a7z|1a7z]], [[209d|209d]], [[1unm|1unm]], [[1i3w|1i3w]], [[1a7y|1a7y]], [[1fja|1fja]], [[173d|173d]], [[2d55|2d55]], [[1dsc|1dsc]], [[1l1v|1l1v]], [[316d|316d]], [[1dsd|1dsd]], [[1unj|1unj]], [[1ovf|1ovf]], [[1qfi|1qfi]]</div></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=1mnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mnv OCA], [https://pdbe.org/1mnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mnv RCSB], [https://www.ebi.ac.uk/pdbsum/1mnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mnv 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=1mnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mnv OCA], [https://pdbe.org/1mnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mnv RCSB], [https://www.ebi.ac.uk/pdbsum/1mnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mnv ProSAT]</span></td></tr> |
| | </table> | | </table> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Actinomyces antibioticus waksman and woodruff 1941]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gao, Y G]] | + | [[Category: Streptomyces antibioticus]] |
| - | [[Category: Hou, M H]] | + | [[Category: Gao Y-G]] |
| - | [[Category: Robinson, H]] | + | [[Category: Hou M-H]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Robinson H]] |
| - | [[Category: Actinomycin]]
| + | [[Category: Wang AH-J]] |
| - | [[Category: Actinomycin d]]
| + | |
| - | [[Category: Anti cancer]]
| + | |
| - | [[Category: Antibiotic]]
| + | |
| - | [[Category: Antitumor]]
| + | |
| - | [[Category: Chromophore]]
| + | |
| - | [[Category: Depsipeptide]]
| + | |
| - | [[Category: Dna-antibiotic complex]]
| + | |
| Structural highlights
Publication Abstract from PubMed
The potent anticancer drug actinomycin D (ActD) acts by binding to DNA GpC sequences, thereby interfering with essential biological processes including replication, transcription and topoisomerase. Certain neurological diseases are correlated with expansion of (CTG)n trinucleotide sequences, which contain many contiguous GpC sites separated by a single base pair. In order to characterize the binding of ActD to CTG triplet repeat sequences, we carried out heat denaturation and CD analyses, which showed that adjacent GpC sequences flanking a T:T mismatch are preferred ActD-binding sites, and that ActD binding results in a conformational transition to A-type structure. The structural basis of the strong binding of ActD to neighboring GpC sites flanking a T:T mismatch was provided by the crystal structure of ActD bound to ATGCTGCAT, which contains a CTG triplet sequence. Binding of two ActD molecules to GCTGC causes a kink in the DNA helix. In addition, using a synthetic self-priming DNA model, 5'-(CAG)4(CTG)(16)-3', we observed that ActD can trap the cruciform or duplexes of (CTG)n and interfere with the expansion process of CTG triplet repeats as shown by gel electrophoretic expansion assay. Our results may provide the possible biological consequence of ActD bound to CTG triplet repeat sequences.
Crystal structure of actinomycin D bound to the CTG triplet repeat sequences linked to neurological diseases.,Hou MH, Robinson H, Gao YG, Wang AH Nucleic Acids Res. 2002 Nov 15;30(22):4910-7. PMID:12433994[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hou MH, Robinson H, Gao YG, Wang AH. Crystal structure of actinomycin D bound to the CTG triplet repeat sequences linked to neurological diseases. Nucleic Acids Res. 2002 Nov 15;30(22):4910-7. PMID:12433994
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