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Crystal structures of a natural DNA polymerase that functions as an XNA reverse transcriptase.
Jackson, Lynnette N; Chim, Nicholas; Shi, Changhua; Chaput, John C.
Afiliación
  • Jackson LN; Departments of Pharmaceutical Sciences, University of California, Irvine, CA 92697-3958, USA.
  • Chim N; Departments of Pharmaceutical Sciences, University of California, Irvine, CA 92697-3958, USA.
  • Shi C; Departments of Pharmaceutical Sciences, University of California, Irvine, CA 92697-3958, USA.
  • Chaput JC; Departments of Pharmaceutical Sciences, University of California, Irvine, CA 92697-3958, USA.
Nucleic Acids Res ; 47(13): 6973-6983, 2019 07 26.
Article en En | MEDLINE | ID: mdl-31170294
Replicative DNA polymerases are highly efficient enzymes that maintain stringent geometric control over shape and orientation of the template and incoming nucleoside triphosphate. In a surprising twist to this paradigm, a naturally occurring bacterial DNA polymerase I member isolated from Geobacillus stearothermophilus (Bst) exhibits an innate ability to reverse transcribe RNA and other synthetic congeners (XNAs) into DNA. This observation raises the interesting question of how a replicative DNA polymerase is able to recognize templates of diverse chemical composition. Here, we present crystal structures of natural Bst DNA polymerase that capture the post-translocated product of DNA synthesis on templates composed entirely of 2'-deoxy-2'-fluoro-ß-d-arabino nucleic acid (FANA) and α-l-threofuranosyl nucleic acid (TNA). Analysis of the enzyme active site reveals the importance of structural plasticity as a possible mechanism for XNA-dependent DNA synthesis and provides insights into the construction of variants with improved activity.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Geobacillus stearothermophilus / Proteínas Bacterianas / ADN Polimerasa Dirigida por ARN / ADN Polimerasa I Idioma: En Revista: Nucleic Acids Res Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Geobacillus stearothermophilus / Proteínas Bacterianas / ADN Polimerasa Dirigida por ARN / ADN Polimerasa I Idioma: En Revista: Nucleic Acids Res Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido