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1lu5

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[[Image:1lu5.gif|left|200px]]
 
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==2.4 Angstrom Crystal Structure of the Asymmetric Platinum Complex {Pt(ammine)(cyclohexylamine)}2+ Bound to a Dodecamer DNA Duplex==
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The line below this paragraph, containing "STRUCTURE_1lu5", creates the "Structure Box" on the page.
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<StructureSection load='1lu5' size='340' side='right'caption='[[1lu5]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1lu5]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LU5 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LPT:CIS-(AMMINE)(CYCLOHEXYLAMINE)PLATINUM(II)+COMPLEX'>LPT</scene></td></tr>
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{{STRUCTURE_1lu5| PDB=1lu5 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lu5 OCA], [https://pdbe.org/1lu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lu5 RCSB], [https://www.ebi.ac.uk/pdbsum/1lu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lu5 ProSAT]</span></td></tr>
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</table>
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'''2.4 Angstrom Crystal Structure of the Asymmetric Platinum Complex {Pt(ammine)(cyclohexylamine)}2+ Bound to a Dodecamer DNA Duplex'''
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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==Overview==
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[[Category: Bu W]]
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cis-trans-cis-Ammine(cyclohexylamine)diacetatodichloroplatinum(IV) is an oral analog of the platinum anti-cancer drug cisplatin that is currently in phase III clinical trials. Its active form, [Pt(ammine)(cyclohexylamine)]2+, binds to DNA similarly to cisplatin, forming intra- and interstrand cross-links between adjacent purine bases. Since [Pt(ammine)(cyclohexylamine)]2+ contains two different ligands, it can form two isomeric 1,2-d(GpG) intrastrand cross-links. Here we report the 2.4-A resolution x-ray crystal structure of the major adduct between [Pt(ammine)(cyclohexylamine)]2+ and a DNA dodecamer, using the same sequence as previously reported for crystal structures of cisplatin-DNA (Takahara, P. M., Rosenzweig, A. C., Frederick, C. A., and Lippard, S. J. (1995) Nature 377, 649-652) and oxaliplatin-DNA (Spingler, B., Whittington, D. A., and Lippard, S. J. (2001) Inorg. Chem. 40, 5596-5602). Both duplexes in the asymmetric unit contain 1,2-intrastrand cross-links in which the cyclohexylamine ligand is directed toward the 3'-end of the platinated strand. The chair conformation of the cyclohexyl group is clearly resolved. Platination distorts the duplex, resulting in a global bend angle of about 38(o) and a dihedral angle between platinated guanine bases of approximately 31(o). Both end-to-end and end-to-groove packing interactions occur in the crystal lattice, the latter positioned in the minor groove across from the site of the platinum cross-link. A high degree of homology observed between this structure and the previously reported platinum-DNA structures suggests that these platinum complexes distort the DNA duplex in a very similar manner. These results suggest that differences in activity between these drugs are unlikely to result from gross conformational distortions in DNA structure following platinum intrastrand cross-link formation.
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[[Category: Cohen SM]]
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[[Category: Lippard SJ]]
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==About this Structure==
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[[Category: Silverman AP]]
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LU5 OCA].
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==Reference==
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2.4-A crystal structure of the asymmetric platinum complex [Pt(ammine)(cyclohexylamine)]2+ bound to a dodecamer DNA duplex., Silverman AP, Bu W, Cohen SM, Lippard SJ, J Biol Chem. 2002 Dec 20;277(51):49743-9. Epub 2002 Oct 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12377787 12377787]
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[[Category: Bu, W.]]
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[[Category: Cohen, S M.]]
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[[Category: Lippard, S J.]]
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[[Category: Silverman, A P.]]
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[[Category: Platinum-dna complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:17:39 2008''
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Current revision

2.4 Angstrom Crystal Structure of the Asymmetric Platinum Complex {Pt(ammine)(cyclohexylamine)}2+ Bound to a Dodecamer DNA Duplex

PDB ID 1lu5

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