6mu4 Citations

Crystal structures of a natural DNA polymerase that functions as an XNA reverse transcriptase.

Nucleic Acids Res 47 6973-6983 (2019)
Cited: 13 times
EuropePMC logo PMID: 31170294

Abstract

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.

Articles - 6mu4 mentioned but not cited (2)

  1. Crystal structures of a natural DNA polymerase that functions as an XNA reverse transcriptase. Jackson LN, Chim N, Shi C, Chaput JC. Nucleic Acids Res 47 6973-6983 (2019)
  2. Crystal structure of DNA polymerase I from Thermus phage G20c. Ahlqvist J, Linares-Pastén JA, Jasilionis A, Welin M, Håkansson M, Svensson LA, Wang L, Watzlawick H, Ævarsson A, Friðjónsson ÓH, Hreggviðsson GÓ, Ketelsen Striberny B, Glomsaker E, Lanes O, Al-Karadaghi S, Nordberg Karlsson E. Acta Crystallogr D Struct Biol 78 1384-1398 (2022)


Reviews citing this publication (2)

  1. Modified nucleic acids: replication, evolution, and next-generation therapeutics. Duffy K, Arangundy-Franklin S, Holliger P. BMC Biol 18 112 (2020)
  2. Thermophilic Nucleic Acid Polymerases and Their Application in Xenobiology. Wang G, Du Y, Ma X, Ye F, Qin Y, Wang Y, Xiang Y, Tao R, Chen T. Int J Mol Sci 23 14969 (2022)

Articles citing this publication (9)

  1. One-Enzyme Reverse Transcription qPCR Using Taq DNA Polymerase. Bhadra S, Maranhao AC, Paik I, Ellington AD. Biochemistry 59 4638-4645 (2020)
  2. 2'-fluoro-modified pyrimidines enhance affinity of RNA oligonucleotides to HIV-1 reverse transcriptase. Gruenke PR, Alam KK, Singh K, Burke DH. RNA 26 1667-1679 (2020)
  3. In Vitro Selection of an ATP-Binding TNA Aptamer. Zhang L, Chaput JC. Molecules 25 E4194 (2020)
  4. Structural Studies of HNA Substrate Specificity in Mutants of an Archaeal DNA Polymerase Obtained by Directed Evolution. Samson C, Legrand P, Tekpinar M, Rozenski J, Abramov M, Holliger P, Pinheiro VB, Herdewijn P, Delarue M. Biomolecules 10 E1647 (2020)
  5. Crystallographic analysis of engineered polymerases synthesizing phosphonomethylthreosyl nucleic acid. Hajjar M, Chim N, Liu C, Herdewijn P, Chaput JC. Nucleic Acids Res 50 9663-9674 (2022)
  6. Modified nucleoside triphosphates in bacterial research for in vitro and live-cell applications. Espinasse A, Lembke HK, Cao AA, Carlson EE. RSC Chem Biol 1 333-351 (2020)
  7. Loop-Mediated Isothermal Amplification: From Theory to Practice. Shirshikov FV, Bespyatykh JA. Russ J Bioorg Chem 48 1159-1174 (2022)
  8. Reverse transcriptase-free detection of viral RNA using Hemo Klentaq DNA polymerase. Sakhabutdinova AR, Gazizov RR, Chemeris AV, Garafutdinov RR. Anal Biochem 659 114960 (2022)
  9. Detection of Specific RNA Targets by Multimerization. Sakhabutdinova AR, Chemeris AV, Garafutdinov RR. Biochemistry (Mosc) 88 679-686 (2023)