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| - | [[Image:2gb9.gif|left|200px]] | |
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| - | {{Structure
| + | ==d(CGTACG)2 crosslinked bis-acridine complex== |
| - | |PDB= 2gb9 |SIZE=350|CAPTION= <scene name='initialview01'>2gb9</scene>, resolution 1.70Å
| + | <StructureSection load='2gb9' size='340' side='right'caption='[[2gb9]], [[Resolution|resolution]] 1.70Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=A4C:9,9'-(HEXANE-1,6-DIYLDIIMINO)BIS{N-[2-(DIMETHYLAMINO)ETHYL]ACRIDINE-4-CARBOXAMIDE}'>A4C</scene>, <scene name='pdbligand=DA:2'-DEOXYADENOSINE-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</scene> | + | <table><tr><td colspan='2'>[[2gb9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GB9 FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A4C:9,9-(HEXANE-1,6-DIYLDIIMINO)BIS{N-[2-(DIMETHYLAMINO)ETHYL]ACRIDINE-4-CARBOXAMIDE}'>A4C</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gb9 OCA], [https://pdbe.org/2gb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gb9 RCSB], [https://www.ebi.ac.uk/pdbsum/2gb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gb9 ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gb9 OCA], [http://www.ebi.ac.uk/pdbsum/2gb9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gb9 RCSB]</span>
| + | __TOC__ |
| - | }}
| + | </StructureSection> |
| - | | + | [[Category: Large Structures]] |
| - | '''d(CGTACG)2 crosslinked bis-acridine complex'''
| + | [[Category: Brogden AL]] |
| - | | + | [[Category: Cardin CJ]] |
| - | | + | [[Category: Hopcroft NH]] |
| - | ==Overview==
| + | [[Category: Searcey M]] |
| - | Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 A resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)2 molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation.
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| - | | + | |
| - | ==About this Structure==
| + | |
| - | 2GB9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GB9 OCA].
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| - | | + | |
| - | ==Reference==
| + | |
| - | X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)2 molecules by a bis(9-aminoacridine-4-carboxamide) derivative., Hopcroft NH, Brogden AL, Searcey M, Cardin CJ, Nucleic Acids Res. 2006;34(22):6663-72. Epub 2006 Dec 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17145714 17145714]
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| - | [[Category: Protein complex]] | + | |
| - | [[Category: Brogden, A L.]] | + | |
| - | [[Category: Cardin, C J.]] | + | |
| - | [[Category: Hopcroft, N H.]] | + | |
| - | [[Category: Searcey, M.]] | + | |
| - | [[Category: dna duplex crosslinking]]
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| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:14:21 2008''
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