2jpz

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(New page: 200px<br /><applet load="2jpz" size="350" color="white" frame="true" align="right" spinBox="true" caption="2jpz" /> '''Structure of the hybrid-2 type intramolecula...)
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==Overview==
==Overview==
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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.
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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 Structure==
==About this Structure==
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[[Category: quadruplex]]
[[Category: quadruplex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:50:53 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:05:02 2008''

Revision as of 16:05, 21 February 2008

Image:2jpz.gif

2jpz

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Structure of the hybrid-2 type intramolecular human telomeric G-quadruplex

Overview

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 Structure

2JPZ is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

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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