2jpz
Structure of the hybrid-2 type intramolecular human telomeric G-quadruplex
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OverviewOverview
Formation of the G-quadruplex in the human telomeric sequence can inhibit, the activity of telomerase, thus the intramolecular telomeric, G-quadruplexes have been considered as an attractive anticancer target., Information of intramolecular telomeric G-quadruplex structures formed, under physiological conditions is important for structure-based drug, design. Here, we report the first structure of the major intramolecular, G-quadruplex formed in a native, non-modified human telomeric sequence in, K(+) solution. This is a hybrid-type mixed, parallel/antiparallel-G-stranded G-quadruplex, one end of which is covered, by a novel T:A:T triple capping structure. This structure (Hybrid-2) and, the previously reported Hybrid-1 structure differ in their loop, arrangements, strand orientations and capping structures. The distinct, capping structures appear to be crucial for the favored formation of the, specific hybrid-type intramolecular telomeric G-quadruplexes, and may, provide specific binding sites for drug targeting. Our study also shows, that while the hybrid-type G-quadruplexes appear to be the major, conformations in K(+) solution, human telomeric sequences are always in, equilibrium between Hybrid-1 and Hybrid-2 structures, which is largely, determined by the 3'-flanking sequence. Furthermore, both hybrid-type, G-quadruplexes suggest a straightforward means for multimer formation with, effective packing in the human telomeric sequence and provide important, implications for drug targeting of G-quadruplexes in human telomeres.
About this StructureAbout this Structure
2JPZ is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence., Dai J, Carver M, Punchihewa C, Jones RA, Yang D, Nucleic Acids Res. 2007;35(15):4927-40. Epub 2007 Jul 10. PMID:17626043
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