Conformational Morphing by a DNA Analogue Featuring 7-Deazapurines and 5-Halogenpyrimidines and the Origins of Adenine-Tract Geometryстатья из журнала
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Библиографическое описание: Conformational Morphing by a DNA Analogue Featuring 7-Deazapurines and 5-Halogenpyrimidines and the Origins of Adenine-Tract Geometry : научное издание / Pradeep S. Pallan [et al.]. - Текст : непосредственный // Biochemistry. - 2023. - Т. 62, № 19. - P. 2854-2867. - ISSN 0006-2960. - ISSN 1520-4995, DOI 10.1021/acs.biochem.3c00327.
Аннотация: Several efforts are currently directed at the creation and cellular implementation of alternative genetic systems composed of pairing components that are orthogonal to the natural dA/dT and dG/dC base pairs. In an alternative approach, Watson–Crick-type pairing is conserved, but one or all of the four letters of the A, C, G, and T alphabet are substituted by modified components. Thus, all four nucleobases were altered to create halogenated deazanucleic acid (DZA): dA was replaced by 7-deaza-2′-deoxyadenosine (dzA), dG by 7-deaza-2′-deoxyguanosine (dzG), dC by 5-fluoro-2′-deoxycytidine (FdC), and dT by 5-chloro-2′-deoxyuridine (CldU). This base-pairing system was previously shown to retain function in Escherichia coli. Here, we analyze the stability, hydration, structure, and dynamics of a DZA Dickerson–Drew Dodecamer (DDD) of sequence 5′-FdC-dzG-FdC-dzG-dzA-dzA-CldU-CldU-FdC-dzG-FdC-dzG-3′. Contrary to similar stabilities of DDD and DZA-DDD, osmotic stressing revealed a dramatic loss of hydration for the DZA-DDD relative to that for the DDD. The parent DDD 5′-d(CGCGAATTCGCG)-3′ features an A-tract, a run of adenosines uninterrupted by a TpA step, and exhibits a hallmark narrow minor groove. Crystal structures─in the presence of RNase H─and MD simulations show increased conformational plasticity ("morphing") of DZA-DDD relative to that of the DDD. The narrow dzA-tract minor groove in one structure widens to resemble that in canonical B-DNA in a second structure. These changes reflect an indirect consequence of altered DZA major groove electrostatics (less negatively polarized compared to that in DNA) and hydration (reduced compared to that in DNA). Therefore, chemical modifications outside the minor groove that lead to collapse of major groove electrostatics and hydration can modulate A-tract geometry.
Год издания: 2023
Авторы: Pallan Pradeep S. , Lybrand Terry P. , Rozners Eriks , Abramov Mikhail , Schepers Guy , Eremeeva Elena , Herdewijn Piet , Egli Martin
Издательство: American Chemical Society
Источник: Biochemistry
Выпуск: Т. 62, № 19
Номера страниц: 2854-2867
Держатель оригинала документа: Department of Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, United States, Department of Chemistry, Binghamton University, Binghamton, New York 13902, United States, Laboratory of Medicinal Chemistry, KU Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, Leuven 3000, Belgium, School of Medicine, Department of Biochemistry, and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, United States
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Твёрдая копия издания отсутствует в фонде библиотеки
Классификационные коды: ГРНТИ 31
ISSN: 0006-2960
Идентификаторы: шифр 63203604