Crystal structures of a natural DNA polymerase that functions as an XNA reverse transcriptase.
Arabinonucleotides
/ metabolism
Bacterial Proteins
/ chemistry
Catalytic Domain
Crystallography, X-Ray
DNA Polymerase I
/ chemistry
DNA, Bacterial
/ metabolism
Geobacillus stearothermophilus
/ enzymology
Models, Molecular
Nucleic Acid Hybridization
Nucleosides
/ metabolism
Protein Binding
Protein Conformation
RNA-Directed DNA Polymerase
/ chemistry
Structure-Activity Relationship
Templates, Genetic
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
26 07 2019
26 07 2019
Historique:
accepted:
03
06
2019
revised:
24
05
2019
received:
29
04
2019
pubmed:
7
6
2019
medline:
7
1
2020
entrez:
7
6
2019
Statut:
ppublish
Résumé
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-β-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.
Identifiants
pubmed: 31170294
pii: 5512092
doi: 10.1093/nar/gkz513
pmc: PMC6649750
doi:
Substances chimiques
2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid
0
Arabinonucleotides
0
Bacterial Proteins
0
DNA, Bacterial
0
Nucleosides
0
alpha-L-threofuranosyl nucleoside triphosphate
0
RNA-Directed DNA Polymerase
EC 2.7.7.49
DNA Polymerase I
EC 2.7.7.7
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
6973-6983Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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