1lu5

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|PDB= 1lu5 |SIZE=350|CAPTION= <scene name='initialview01'>1lu5</scene>, resolution 2.40&Aring;
|PDB= 1lu5 |SIZE=350|CAPTION= <scene name='initialview01'>1lu5</scene>, resolution 2.40&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=LPT:CIS-(AMMINE)(CYCLOHEXYLAMINE)PLATINUM(II) COMPLEX'>LPT</scene>
+
|LIGAND= <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=LPT:CIS-(AMMINE)(CYCLOHEXYLAMINE)PLATINUM(II)+COMPLEX'>LPT</scene>
|ACTIVITY=
|ACTIVITY=
|GENE=
|GENE=
 +
|DOMAIN=
 +
|RELATEDENTRY=
 +
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lu5 OCA], [http://www.ebi.ac.uk/pdbsum/1lu5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lu5 RCSB]</span>
}}
}}
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[[Category: Lippard, S J.]]
[[Category: Lippard, S J.]]
[[Category: Silverman, A P.]]
[[Category: Silverman, A P.]]
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[[Category: LPT]]
 
[[Category: platinum-dna complex]]
[[Category: platinum-dna complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:35:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:07:26 2008''

Revision as of 19:07, 30 March 2008


PDB ID 1lu5

Drag the structure with the mouse to rotate
, resolution 2.40Å
Ligands: , , , ,
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



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


Overview

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.

About this Structure

1LU5 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

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:12377787

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