193D

SOLUTION STRUCTURE OF A QUINOMYCIN BISINTERCALATOR-DNA COMPLEX

Summary for 193D

• Entry DOI: 10.2210/pdb193d/pdb
• Related: 185D 1PFE 1VS2 1XVK 1XVN 1XVR 2ADW 2DA8 3GO3
• Related PRD ID: PRD_000492
• Descriptor: DNA (5'-D(*AP*CP*AP*CP*GP*TP*GP*T)-3'), QUINOMYCIN, 3-HYDROXYQUINALDIC ACID (3 entities in total)
• Functional Keywords: bisintercalator, depsipeptide, quinoxaline, thioacetal, antibiotic, antitumor, dna-antibiotic complex, dna/antibiotic
• Total number of polymer chains: 3
• Total formula weight: 6078.62

Authors

Chen, H.,Patel, D.J. (deposition date: 1994-09-30, release date: 1995-02-27, Last modification date: 2017-11-01)

Primary citation

Chen, H.,Patel, D.J.
Solution Structure of a Quinomycin Bisintercalator-DNA Complex.
J.Mol.Biol., 246:164-, 1995

PubMed Abstract: The quinomycin antibiotic UK-63052 (designated QN) exhibits a chemical structure related to the antibiotic echinomycin which is known to bisintercalate into DNA. Common features among these antibiotics include two heterocyclic aromatic ring systems propagating from a cross-bridged cyclic octadepsipeptide scaffold. We report on the solution structure of the QN-d(A1-C2-A3-C4-G5-T6-G7-T8) complex (one QN molecule per duplex) based on a combined NMR-molecular dynamics study including intensity-based refinement. The 3-hydroxy quinaldic acid rings bisintercalate into the duplex at (A3-C4).(G5-T6) steps and stack with flanking Watson-Crick A3.T6 and C4.G5 base-pairs. The intercalation sites at (A3-C4).(G5-T6) steps are wedge-shaped and unwound, with significant unwinding also observed at the (C4-C5).(C4-G5) step bracketed between the intercalation sites. The cross-bridged cyclic octadepsipeptide is positioned in the minor groove with the methyl groups on its Ala and NMe-MCp residues directed towards and making van der Waals contacts with the minor groove edge of the duplex. A pair of adjacent intermolecular hydrogen bonds between the Ala backbone atoms and the G5 minor groove edge (Ala-NH to G5-N(3) and G5-NH2e to Ala-CO) account for the sequence specificity associated with complex formation. The solution structure of the QN-DNA oligomer complex, which contains only Watson-Crick base-pairs flanking the bisintercalation site, is compared with the crystal structure of the related echinomycin-DNA oligomer complex, which contains Hoogsteen base-pairs on either side of the bisintercalation site.

PubMed: 7853395
DOI: 10.1006/JMBI.1994.0074

Experimental method

SOLUTION NMR