3TVB

A Highly Symmetric DNA G-4 Quadruplex/drug Complex

Summary for 3TVB

• Entry DOI: 10.2210/pdb3tvb/pdb
• Descriptor: DNA (5'-D(*GP*GP*GP*G)-3'), DAUNOMYCIN, SODIUM ION, ... (5 entities in total)
• Functional Keywords: g-4 quadruplex, daunomycin, dna-drug complex, dna-antibiotic complex, dna/antibiotic
• Total number of polymer chains: 2
• Total formula weight: 4886.34

Authors

Clark, G.R.,Pytel, P.D.,Squire, C.J. (deposition date: 2011-09-19, release date: 2012-03-14, Last modification date: 2024-02-28)

Primary citation

Clark, G.R.,Pytel, P.D.,Squire, C.J.
The high-resolution crystal structure of a parallel intermolecular DNA G-4 quadruplex/drug complex employing syn glycosyl linkages.
Nucleic Acids Res., 40:5731-5738, 2012

PubMed Abstract: We have determined the X-ray structure of the complex between the DNA quadruplex d(5'-GGGG-3')(4) and daunomycin, as a potential model for studying drug-telomere interactions. The structure was solved at 1.08 Å by direct methods in space group I4. The asymmetric unit comprises a linear arrangement of one d(GGGG) strand, four daunomycin molecules, a second d(GGGG) strand facing in the opposite direction to the first, and Na and Mg cations. The crystallographic 4-fold axis generates the biological unit, which is a 12-layered structure comprising two sets of four guanine layers, with four layers each of four daunomycins stacked between the 5' faces of the two quadruplexes. The daunomycin layers fall into two groups which are novel in their mode of self assembly. The only contacts between daunomycin molecules within any one of these layers are van der Waals interactions, however there is substantial π-π stacking between successive daunomycin layers and also with adjacent guanine layers. The structure differs significantly from all other parallel d(TGGGGT)(4) quadruplexes in that the 5' guanine adopts the unusual syn glycosyl linkage, refuting the widespread belief that such conformations should all be anti. In contrast to the related d(TGGGGT)/daunomycin complex, there are no ligand-quadruplex groove insertion interactions.

PubMed: 22373921
DOI: 10.1093/nar/gks193

Experimental method

X-RAY DIFFRACTION (1.08 Å)