publication . Article . Other literature type . Conference object . 2020

Crucial Roles of Two Hydrated Mg 2+ Ions in Reaction Catalysis of the Pistol Ribozyme

Teplova, Marianna; Falschlunger, Christoph; Krasheninina, Olga; Egger, Michaela; Ren, Aiming; Patel, Dinshaw J.; Micura, Ronald;
Open Access
  • Published: 10 Feb 2020 Journal: Angewandte Chemie, volume 132, pages 2,859-2,865 (issn: 0044-8249, eissn: 1521-3757, Copyright policy)
  • Publisher: Wiley
Abstract
Abstract Pistol ribozymes constitute a new class of small self‐cleaving RNAs. Crystal structures have been solved, providing three‐dimensional snapshots along the reaction coordinate of pistol phosphodiester cleavage, corresponding to the pre‐catalytic state, a vanadate mimic of the transition state, and the product. The results led to the proposed underlying chemical mechanism. Importantly, a hydrated Mg2+ ion remains innersphere‐coordinated to N7 of G33 in all three states, and is consistent with its likely role as acid in general acid base catalysis (δ and β catalysis). Strikingly, the new structures shed light on a second hydrated Mg2+ ion that approaches th...
Subjects
free text keywords: General Medicine, General Chemistry, Catalysis, Research Article, Research Articles, RNA, magnesium, oligonucleotides, reaction mechanisms, structure–function relationships
Funded by
FWF| Chemical synthesis of modified twister ribozymes
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: P 27947
  • Funding stream: Einzelprojekte
,
NIH| MOUSE GENETICS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
,
FWF| Understanding hatchet ribozymes
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: P 31691
  • Funding stream: Einzelprojekte
,
NIH| Biochemical and structural characterization of RNA turnover processes and resolu
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U19CA179564-02
  • Funding stream: NATIONAL CANCER INSTITUTE
,
FWF| Novel synthetic pathways to cyclic oligoribonucleotides
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: M 2517
  • Funding stream: Meitner-Programm
39 references, page 1 of 3

1 R. M.Jimenez, J. A.Polanco, A.Lupták, Trends Biochem. Sci.2015, 40, 648–661.26481500 [OpenAIRE] [PubMed]

2 A.Ren, R.Micura, D. J.Patel, Curr. Opin. Chem. Biol.2017, 41, 71–83.29107885 [PubMed]

3 E.Westhof, Genome Biol.2010, 11, 108.20236470 [OpenAIRE] [PubMed]

4 P. C.Bevilacqua, R.Yajima, Curr. Opin. Chem. Biol.2006, 10, 455–464.16935552 [PubMed]

5 P. C.Bevilacqua, M. E.Harris, J. A.Piccirilli, C.Gaines, A.Ganguly, K.Kostenbader, Ş.Ekesan, D. M.York, ACS Chem. Biol.2019, 14, 1068–1076.31095369 [OpenAIRE] [PubMed]

6 R.Hieronymus, S.Müller, Ann. N. Y. Acad. Sci.2019, 1447, 135–143.30941784 [PubMed]

7 A. R.Ferré-D'Amaré, W. G.Scott, Cold Spring Harbor Perspect. Biol.2010, 2, a 003574.

8 C.Reymond, J. D.Beaudoin, J. P.Perreault, Cell. Mol. Life Sci.2009, 66, 3937–3950.19718544 [OpenAIRE] [PubMed]

9 M. J.Fedor, Annu. Rev. Biophys.2009, 38, 271–299.19416070 [PubMed]

10 J. C.Cochrane, S. A.Strobel, Acc. Chem. Res.2008, 41, 1027–1035.18652494 [OpenAIRE] [PubMed]

11 M.de la Peña, Adv. Exp. Med. Biol.2018, 1087, 53–63.30259357 [PubMed]

12 M.Felletti, J. S.Hartig, Wiley Interdiscip. Rev. RNA 2017, 8, e1395.

13 S.Kath-Schorr, T. J.Wilson, N.-S.Li, J.Lu, J. A.Piccirilli, D. M. J.Lilley, J. Am. Chem. Soc.2012, 134, 16717–16724.22958171 [OpenAIRE] [PubMed]

14 A.Roth, Z.Weinberg, A. G. Y.Chen, P. B.Kim, T. D.Ames, R. R.Breaker, Nat. Chem. Biol.2014, 10, 56–60.24240507 [OpenAIRE] [PubMed]

15 Z.Weinberg, P. B.Kim, T. H.Chen, S.Li, K. A.Harris, C. E.Lünse, R. R.Breaker, Nat. Chem. Biol.2015, 11, 606–610.26167874 [OpenAIRE] [PubMed]

39 references, page 1 of 3
Abstract
Abstract Pistol ribozymes constitute a new class of small self‐cleaving RNAs. Crystal structures have been solved, providing three‐dimensional snapshots along the reaction coordinate of pistol phosphodiester cleavage, corresponding to the pre‐catalytic state, a vanadate mimic of the transition state, and the product. The results led to the proposed underlying chemical mechanism. Importantly, a hydrated Mg2+ ion remains innersphere‐coordinated to N7 of G33 in all three states, and is consistent with its likely role as acid in general acid base catalysis (δ and β catalysis). Strikingly, the new structures shed light on a second hydrated Mg2+ ion that approaches th...
Subjects
free text keywords: General Medicine, General Chemistry, Catalysis, Research Article, Research Articles, RNA, magnesium, oligonucleotides, reaction mechanisms, structure–function relationships
Funded by
FWF| Chemical synthesis of modified twister ribozymes
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: P 27947
  • Funding stream: Einzelprojekte
,
NIH| MOUSE GENETICS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
,
FWF| Understanding hatchet ribozymes
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: P 31691
  • Funding stream: Einzelprojekte
,
NIH| Biochemical and structural characterization of RNA turnover processes and resolu
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U19CA179564-02
  • Funding stream: NATIONAL CANCER INSTITUTE
,
FWF| Novel synthetic pathways to cyclic oligoribonucleotides
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: M 2517
  • Funding stream: Meitner-Programm
39 references, page 1 of 3

1 R. M.Jimenez, J. A.Polanco, A.Lupták, Trends Biochem. Sci.2015, 40, 648–661.26481500 [OpenAIRE] [PubMed]

2 A.Ren, R.Micura, D. J.Patel, Curr. Opin. Chem. Biol.2017, 41, 71–83.29107885 [PubMed]

3 E.Westhof, Genome Biol.2010, 11, 108.20236470 [OpenAIRE] [PubMed]

4 P. C.Bevilacqua, R.Yajima, Curr. Opin. Chem. Biol.2006, 10, 455–464.16935552 [PubMed]

5 P. C.Bevilacqua, M. E.Harris, J. A.Piccirilli, C.Gaines, A.Ganguly, K.Kostenbader, Ş.Ekesan, D. M.York, ACS Chem. Biol.2019, 14, 1068–1076.31095369 [OpenAIRE] [PubMed]

6 R.Hieronymus, S.Müller, Ann. N. Y. Acad. Sci.2019, 1447, 135–143.30941784 [PubMed]

7 A. R.Ferré-D'Amaré, W. G.Scott, Cold Spring Harbor Perspect. Biol.2010, 2, a 003574.

8 C.Reymond, J. D.Beaudoin, J. P.Perreault, Cell. Mol. Life Sci.2009, 66, 3937–3950.19718544 [OpenAIRE] [PubMed]

9 M. J.Fedor, Annu. Rev. Biophys.2009, 38, 271–299.19416070 [PubMed]

10 J. C.Cochrane, S. A.Strobel, Acc. Chem. Res.2008, 41, 1027–1035.18652494 [OpenAIRE] [PubMed]

11 M.de la Peña, Adv. Exp. Med. Biol.2018, 1087, 53–63.30259357 [PubMed]

12 M.Felletti, J. S.Hartig, Wiley Interdiscip. Rev. RNA 2017, 8, e1395.

13 S.Kath-Schorr, T. J.Wilson, N.-S.Li, J.Lu, J. A.Piccirilli, D. M. J.Lilley, J. Am. Chem. Soc.2012, 134, 16717–16724.22958171 [OpenAIRE] [PubMed]

14 A.Roth, Z.Weinberg, A. G. Y.Chen, P. B.Kim, T. D.Ames, R. R.Breaker, Nat. Chem. Biol.2014, 10, 56–60.24240507 [OpenAIRE] [PubMed]

15 Z.Weinberg, P. B.Kim, T. H.Chen, S.Li, K. A.Harris, C. E.Lünse, R. R.Breaker, Nat. Chem. Biol.2015, 11, 606–610.26167874 [OpenAIRE] [PubMed]

39 references, page 1 of 3
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