1LU5

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

Summary for 1LU5

• Entry DOI: 10.2210/pdb1lu5/pdb
• Descriptor: 5'-D(*CP*CP*TP*CP*TP*GP*GP*TP*CP*TP*CP*C)-3', 5'-D(*GP*GP*AP*GP*AP*CP*CP*AP*GP*AP*GP*G)-3', CIS-(AMMINE)(CYCLOHEXYLAMINE)PLATINUM(II) COMPLEX, ... (4 entities in total)
• Functional Keywords: platinum-dna complex, dna
• Total number of polymer chains: 4
• Total formula weight: 15276.13

Authors

Silverman, A.P.,Bu, W.,Cohen, S.M.,Lippard, S.J. (deposition date: 2002-05-21, release date: 2002-12-20, Last modification date: 2024-02-14)

Primary citation

Silverman, A.P.,Bu, W.,Cohen, S.M.,Lippard, S.J.
2.4-A Crystal Structure of the Asymmetric Platinum Complex {Pt(ammine)(cyclohexylamine)}2+ Bound to a Dodecamer DNA Duplex
J.Biol.Chem., 277:49743-49749, 2002

PubMed Abstract: 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.

PubMed: 12377787
DOI: 10.1074/jbc.M206979200

Experimental method

X-RAY DIFFRACTION (2.4 Å)