PDBsum entry 1dsa

DNA

PDB id: 1dsa

Contents

DNA/RNA

Ligands

DSA

PDB id:

1dsa

Name:

DNA

Title:

(+)-Duocarmycin sa covalently linked to duplex DNA, nmr, 20 structures

Structure:

DNA (5'-d( Gp Ap Cp Tp Ap Ap Tp Tp Gp Ap C)-3', 5'- d( Gp Tp Cp Ap Ap Tp Tp Ap Gp Tp C)-3'). Chain: a. Engineered: yes. DNA (5'-d( Gp Ap Cp Tp Ap Ap Tp Tp Gp Ap C)-3', 5'- d( Gp Tp Cp Ap Ap Tp Tp Ap Gp Tp C)-3'). Chain: b. Engineered: yes

Source:

Synthetic: yes. Synthetic: yes

NMR struc:

20 models

Authors:

P.S.Eis,J.A.Smith,D.A.Case,W.J.Chazin

Key ref:

P.S.Eis et al. (1997). High resolution solution structure of a DNA duplex alkylated by the antitumor agent duocarmycin SA. J Mol Biol, 272, 237-252. PubMed id: 9299351 DOI: 10.1006/jmbi.1997.1223

Date:

08-May-97 Release date: 20-Aug-97

DNA/RNA chains

G-A-C-T-A-A-T-T-G-A-C 11 bases

G-T-C-A-A-T-T-A-G-T-C 11 bases

DOI no: 10.1006/jmbi.1997.1223

J Mol Biol 272:237-252 (1997)

PubMed id: 9299351

High resolution solution structure of a DNA duplex alkylated by the antitumor agent duocarmycin SA.

P.S.Eis, J.A.Smith, J.M.Rydzewski, D.A.Case, D.L.Boger, W.J.Chazin.

ABSTRACT

The three-dimensional solution structure of duocarmycin SA in complex with d-(G1ACTAATTGAC11).d-(G12TCATTAGTC22) has been determined by restrained molecular dynamics and relaxation matrix calculations using experimental NOE distance and torsion angle constraints derived from 1H NMR spectroscopy. The final input data consisted of a total of 858 distance and 189 dihedral angle constraints, an average of 46 constraints per residue. In the ensemble of 20 final structures, there were no distance constraint violations >0.06 A or torsion angle violations >0.8 degrees. The average pairwise root mean square deviation (RMSD) over all 20 structures for the binding site region is 0.57 A (average RMSD from the mean: 0.39 A). Although the DNA is very B-like, the sugar-phosphate backbone torsion angles beta, epsilon, and zeta are distorted from standard values in the binding site region. The structure reveals site-specific bonding of duocarmycin SA at the N3 position of adenine 19 in the AT-rich minor groove of the duplex and binding stabilization via hydrophobic interactions. Comparisons have been made to the structure of a closely related complex of duocarmycin A bound to an AT-rich DNA duplex. These results provide insights into critical aspects of the alkylation site selectivity and source of catalysis of the DNA alkylating agents, and the unusual stability of the resulting adducts.

Selected figure(s)

Figure 12.
Figure 12. Population of two conformations by the DSA methyl ester in the DSA-DNA complex. 65% of the structures occupy the orientation shown in red and the remainder occupy the cyan orientation. The two alter- nate hydrogen bonding interactions are indicated, along with the corresponding distance between T4H10 and DSA O15CH 3.

Figure 14.
Figure 14. Schematic diagram of the alkylation (and back reaction) of an adenine residue by DSA.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 272, 237-252) copyright 1997.

Figures were selected by an automated process.