1l1h
From Proteopedia
Crystal Structure of the Quadruplex DNA-Drug Complex
Overview
Stabilisation of G-quadruplex structures formed from telomeric DNA, by means of quadruplex-selective ligands, is a means of inhibiting the telomerase enzyme from catalysing the synthesis of telomeric DNA repeats. In order to understand the molecular basis of ligand-quadruplex recognition, the crystal structure has been determined of such a complex, at 1.75A resolution. This complex is between a dimeric antiparallel G-quadruplex formed from the Oxytricha nova telomeric DNA sequence d(GGGGTTTTGGGG), and a di-substituted aminoalkylamido acridine compound. The structure shows that the acridine moiety is bound at one end of the stack of G-quartets, within one of the thymine loops. It is held in place by a combination of stacking interactions and specific hydrogen bonds with thymine bases. The stability of the ligand in this binding site has been confirmed by a 2ns molecular dynamics simulation.
About this Structure
Full crystallographic information is available from OCA.
Reference
Structure of a G-quadruplex-ligand complex., Haider SM, Parkinson GN, Neidle S, J Mol Biol. 2003 Feb 7;326(1):117-25. PMID:12547195 Page seeded by OCA on Fri May 2 23:25:59 2008
