1L1H

Crystal Structure of the Quadruplex DNA-Drug Complex

Summary for 1L1H

• Entry DOI: 10.2210/pdb1l1h/pdb
• Descriptor: 5'-D(*GP*GP*GP*GP*TP*TP*TP*TP*GP*GP*GP*G)-3', 3-PYRROLIDIN-1-YL-N-[6-(3-PYRROLIDIN-1-YL-PROPIONYLAMINO)-ACRIDIN-3-YL]-PROPIONAMIDE, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: g-quadruplex, oxytricha, four-stranded dna, dna
• Total number of polymer chains: 2
• Total formula weight: 8226.90

Authors

Haider, S.M.,Parkinson, G.N.,Neidle, S. (deposition date: 2002-02-16, release date: 2003-02-11, Last modification date: 2023-08-16)

Primary citation

Haider, S.M.,Parkinson, G.N.,Neidle, S.
Structure of a G-quadruplex-Ligand Complex
J.Mol.Biol., 326:117-125, 2003

PubMed Abstract: 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.

PubMed: 12547195
DOI: 10.1016/S0022-2836(02)01354-2

Experimental method

X-RAY DIFFRACTION (1.75 Å)