Nucleic acids research
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Nucleic acids research · Jan 2006
Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution.
Human telomeric DNA consists of tandem repeats of the sequence d(TTAGGG). The formation and stabilization of DNA G-quadruplexes in the human telomeric sequence have been shown to inhibit the activity of telomerase, thus the telomeric DNA G-quadruplex has been considered as an attractive target for cancer therapeutic intervention. However, knowledge of the intact human telomeric G-quadruplex structure(s) formed under physiological conditions is a prerequisite for structure-based rational drug design. ⋯ Our results explain all the reported experimental data on the human telomeric G-quadruplexes formed in the presence of K+, and provide important insights for understanding the polymorphism and interconversion of various G-quadruplex structures formed within the human telomeric sequence, as well as the effects of sequence and cations. This hybrid-type G-quadruplex topology suggests a straightforward pathway for the secondary structure formation with effective packing within the extended human telomeric DNA. The hybrid-type telomeric G-quadruplex is most likely to be of pharmacological relevance, and the distinct folding topology of this G-quadruplex suggests that it can be specifically targeted by G-quadruplex interactive small molecule drugs.
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The database, CryptoDB (http://CryptoDB.org), is a community bioinformatics resource for the AIDS-related apicomplexan-parasite, Cryptosporidium. CryptoDB integrates whole genome sequence and annotation with expressed sequence tag and genome survey sequence data and provides supplemental bioinformatics analyses and data-mining tools. ⋯ CryptoDB is allied with the databases PlasmoDB and ToxoDB via ApiDB, an NIH/NIAID-fundedBioinformatics Resource Center. Recent updates to CryptoDB include the deposition of annotated genome sequences for Cryptosporidium parvum and Cryptosporidium hominis, migration to a relational database (GUS), a new query and visualization interface and the introduction of Web services.