Structural basis for binding of porphyrin to human telomeres.
作者： Gary N. Parkinson , Ragini Ghosh , Stephen Neidle
DOI: 10.1021/BI062244N
关键词:
摘要: Maintenance of telomere integrity is a hallmark human cancer, and the single-stranded 3' ends telomeric DNA are targets for small-molecule anticancer therapies. We report here crystal structure bimolecular quadruplex, sequence d(TAGGGTTAGGG), in complex with quadruplex-binding ligand 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) to resolution 2.09 A. The quadruplex topology parallel-stranded external double-chain-reversal propeller loops, consistent previous structural determinations. porphyrin molecules bind by stacking onto TTA nucleotides, either as part loop or at 5' region stacked quadruplex. This involves on hydrogen-bonded base pairs, formed from those nucleotides not involved formation G-tetrads, there thus no direct interactions G-tetrads. accord relative nonselectivity TMPyP4 DNAs compared duplex DNA. Porphyrin binding achieved remodeling loops ligand-free structures. Implications design ligands discussed, together model anaphase bridges, which observed following cellular treatment TMPyP4.
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