1DSA

(+)-DUOCARMYCIN SA COVALENTLY LINKED TO DUPLEX DNA, NMR, 20 STRUCTURES

1DSA の概要

• エントリーDOI: 10.2210/pdb1dsa/pdb
• 分子名称: 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'), 4-HYDROXY-8-METHYL-6-(4,5,6-TRIMETHOXY-1H-INDOLE-2-CARBONYL)-3,6,7,8-TETRAHYDRO-3,6-DIAZA-AS-INDACENE-2-CARBOXYLIC ACID METHYL ESTER (3 entities in total)
• 機能のキーワード: duocarmycin, dna, minor groove binding, antitumor agent, drug-dna complex, deoxyribonucleic acid
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7184.91

構造登録者

Eis, P.S.,Smith, J.A.,Case, D.A.,Chazin, W.J. (登録日: 1997-05-08, 公開日: 1997-08-20, 最終更新日: 2024-05-22)

主引用文献

Eis, P.S.,Smith, J.A.,Rydzewski, J.M.,Case, D.A.,Boger, D.L.,Chazin, W.J.
High resolution solution structure of a DNA duplex alkylated by the antitumor agent duocarmycin SA.
J.Mol.Biol., 272:237-252, 1997

PubMed 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.

PubMed: 9299351
DOI: 10.1006/jmbi.1997.1223

実験手法

SOLUTION NMR