'''2.4 Angstrom Crystal Structure of the Asymmetric Platinum Complex {Pt(ammine)(cyclohexylamine)}2+ Bound to a Dodecamer DNA Duplex'''
===2.4 Angstrom Crystal Structure of the Asymmetric Platinum Complex {Pt(ammine)(cyclohexylamine)}2+ Bound to a Dodecamer DNA Duplex===
==Overview==
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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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==About this Structure==
==About this Structure==
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[[Category: Silverman, A P.]]
[[Category: Silverman, A P.]]
[[Category: Platinum-dna complex]]
[[Category: Platinum-dna complex]]
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Revision as of 19:14, 2 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
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
