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New page: left|200px<br /><applet load="1aio" size="450" color="white" frame="true" align="right" spinBox="true" caption="1aio, resolution 2.600Å" /> '''CRYSTAL STRUCTURE O...
 
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[[Image:1aio.gif|left|200px]]<br /><applet load="1aio" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1aio, resolution 2.600&Aring;" />
'''CRYSTAL STRUCTURE OF A DOUBLE-STRANDED DNA CONTAINING THE MAJOR ADDUCT OF THE ANTICANCER DRUG CISPLATIN'''<br />


==Overview==
==CRYSTAL STRUCTURE OF A DOUBLE-STRANDED DNA CONTAINING THE MAJOR ADDUCT OF THE ANTICANCER DRUG CISPLATIN==
The success of cisplatin in cancer chemotherapy derives from its ability, to crosslink DNA and alter the structure. Most cisplatin-DNA adducts are, intrastrand d(GpG) and d(ApG) crosslinks, which unwind and bend the duplex, to facilitate the binding of proteins that contain one or more, high-mobility group (HMG) domains. When HMG-domain proteins such as HMG1, IXR (intrastrand-crosslink recognition) protein from yeast, or human, upstream-binding factor (hUBF) bind cisplatin intrastrand crosslinks, they, can be diverted from their natural binding sites on the genome and shield, the adducts from excision repair. These activities sensitize cells to, cisplatin and contribute to its cytotoxic properties. Crystallographic, information about the structure of cisplatin-DNA adducts has been limited, to short single-stranded deoxyoligonucleotides such as, cis-[Pt(NH3)2(d(pGpG))]. Here we describe the X-ray structure at 2.6 A, resolution of a double-stranded DNA dodecamer containing this adduct. Our, information provides, to our knowledge, the first crystallographic look at, a platinated DNA duplex and should help the design of new platinum and, other metal crosslinking antitumour drug candidates. Moreover, the, structure reveals a unique fusion of A- and B-type DNA segments that could, be of more general importance.
<StructureSection load='1aio' size='340' side='right'caption='[[1aio]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1aio]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AIO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BRU:5-BROMO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>BRU</scene>, <scene name='pdbligand=CPT:CISPLATIN'>CPT</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=1aio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aio OCA], [https://pdbe.org/1aio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1aio RCSB], [https://www.ebi.ac.uk/pdbsum/1aio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1aio ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The success of cisplatin in cancer chemotherapy derives from its ability to crosslink DNA and alter the structure. Most cisplatin-DNA adducts are intrastrand d(GpG) and d(ApG) crosslinks, which unwind and bend the duplex to facilitate the binding of proteins that contain one or more high-mobility group (HMG) domains. When HMG-domain proteins such as HMG1, IXR (intrastrand-crosslink recognition) protein from yeast, or human upstream-binding factor (hUBF) bind cisplatin intrastrand crosslinks, they can be diverted from their natural binding sites on the genome and shield the adducts from excision repair. These activities sensitize cells to cisplatin and contribute to its cytotoxic properties. Crystallographic information about the structure of cisplatin-DNA adducts has been limited to short single-stranded deoxyoligonucleotides such as cis-[Pt(NH3)2(d(pGpG))]. Here we describe the X-ray structure at 2.6 A resolution of a double-stranded DNA dodecamer containing this adduct. Our information provides, to our knowledge, the first crystallographic look at a platinated DNA duplex and should help the design of new platinum and other metal crosslinking antitumour drug candidates. Moreover, the structure reveals a unique fusion of A- and B-type DNA segments that could be of more general importance.


==About this Structure==
Crystal structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatin.,Takahara PM, Rosenzweig AC, Frederick CA, Lippard SJ Nature. 1995 Oct 19;377(6550):649-52. PMID:7566180<ref>PMID:7566180</ref>
1AIO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with CPT as [http://en.wikipedia.org/wiki/ligand ligand]. This structure superseeds the now removed PDB entry 1GPG. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AIO OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatin., Takahara PM, Rosenzweig AC, Frederick CA, Lippard SJ, Nature. 1995 Oct 19;377(6550):649-52. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7566180 7566180]
</div>
[[Category: Protein complex]]
<div class="pdbe-citations 1aio" style="background-color:#fffaf0;"></div>
[[Category: Frederick, C.A.]]
== References ==
[[Category: Lippard, S.J.]]
<references/>
[[Category: Rosenzweig, A.C.]]
__TOC__
[[Category: Takahara, P.M.]]
</StructureSection>
[[Category: CPT]]
[[Category: Large Structures]]
[[Category: complexed with drug]]
[[Category: Frederick CA]]
[[Category: double helix]]
[[Category: Lippard SJ]]
[[Category: modified]]
[[Category: Rosenzweig AC]]
[[Category: right handed dna]]
[[Category: Takahara PM]]
 
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Latest revision as of 05:22, 13 August 2026

CRYSTAL STRUCTURE OF A DOUBLE-STRANDED DNA CONTAINING THE MAJOR ADDUCT OF THE ANTICANCER DRUG CISPLATIN

1aio, resolution 2.60Å

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