Summary information and primary citation
- PDB-id
-
193d;
SNAP-derived features in text and
JSON formats
- Class
- DNA-antibiotic
- Method
- NMR
- Summary
- Solution structure of a quinomycin bisintercalator-DNA
complex
- Reference
-
Chen H, Patel DJ (1995): "Solution
Structure of a Quinomycin Bisintercalator-DNA
Complex." J.Mol.Biol., 246,
164. doi: 10.1006/JMBI.1994.0074.
- 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.
