NDLI: Distamycin A modulates the sequence specificity of DNA alkylation by duocarmycin A.

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Mapping the universe in three dimensions.

Astrophysical symmetries.

A brief survey of symmetry in mathematics.

Convex polytopes and quantization of symplectic manifolds.

The role of symmetry in fundamental physics.

Symmetries in geology and geophysics.

Symmetries throughout the sciences. Concluding talk.

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Symmetries throughout organic evolution.

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Distamycin A modulates the sequence specificity of DNA alkylation by duocarmycin A.

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Distamycin A modulates the sequence specificity of DNA alkylation by duocarmycin A.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sugiyama, H. Lian, C. Isomura, M. Saito, I. Wang, A. H.
Description	Author Affiliation: Sugiyama H ( Department of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering, Kyoto University, Japan.);
Abstract	Duocarmycin A (Duo) normally alkylates adenine N3 at the 3' end of A + T-rich sequences in DNA. The efficient adenine alkylation by Duo is achieved by its monomeric binding to the DNA minor groove. The addition of another minor groove binder, distamycin A (Dist), dramatically modulates the site of DNA alkylation by Duo, and the alkylation switches preferentially to G residues in G + C-rich sequences. HPLC product analysis using oligonucleotides revealed a highly efficient G-N3 alkylation via the cooperative binding of a heterodimer between Duo and Dist to the minor groove. The three-dimensional structure of the ternary alkylated complex of Duo/Dist/d(CAGGTGGT).d(ACCACCTG) has been determined by nuclear Overhauser effect (NOE)-restrained refinement using 750 MHz two-dimensional NOE spectroscopy data. The refined NMR structure fully explains the sequence requirement of such modulated alkylations. This is the first demonstration of Duo DNA alkylation through cooperative binding with another structurally different natural product, and it suggests a promising new way to alter or modify the DNA alkylation selectivity in a predictable manner.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	25
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA Metabolism Distamycins Indoles Alkylation Chemistry Genetics Models, Molecular Protein Conformation Pyrrolidinones Sequence Analysis, DNA Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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