1d33

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spinqualitylabelsall models 1d33, resolution 1.500Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

FORMALDEHYDE CROSS-LINKS DAUNORUBICIN AND DNA EFFICIENTLY: HPLC AND X-RAY DIFFRACTION STUDIES

Overview

Formaldehyde (HCHO) cross-links the anticancer drug daunorubicin (DAU) to, DNA efficiently. When DAU is mixed with DNA hexamers, d(CGCGCG) and, d(CGTDCG), in the presence of HCHO, stable covalent adducts of DNA are, formed, as shown by the HPLC analyses. The major adducts are identical, with the materials in the respective crystals which can be readily, obtained from the 1:1 mixture of DAU-d(CGCGCG) and DAU-d(CGTDCG) plus, HCHO, but not from the solution without HCHO. The high-resolution (1.5 A), X-ray crystal structure of those adducts shows unambiguously that they, contain a covalent methylene bridge between the N3' of daunosamine and the, N2 of the guanine or 2-aminoadenine. The perfect juxtaposition of the two, amino groups in the minor groove of the complex provides a template for an, efficient addition of HCHO. The methylene bridge does not perturb the, conformation of the drug-DNA complex, when compared to the structure of, DAU-d(CGTACG). The results suggest new approaches for synthesizing a new, type of potential anticancer drug by attaching a reactive (e.g., alkylating) functional group at the N3' amino position of, daunorubicin/doxorubicin. The stable drug-DNA adduct may be useful as, probes for other biological studies.

About this Structure

1D33 is a Protein complex structure of sequences from [1] with DM1 and MG as ligands. Full crystallographic information is available from OCA.

Reference

Formaldehyde cross-links daunorubicin and DNA efficiently: HPLC and X-ray diffraction studies., Wang AH, Gao YG, Liaw YC, Li YK, Biochemistry. 1991 Apr 23;30(16):3812-5. PMID:2018756

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