An Ontology for Facilitating Discussion of Catalytic Strategies of RNA-Cleaving Enzymes

Philip C. Bevilacqua, Michael E. Harris, Joseph A. Piccirilli, Colin Gaines, Abir Ganguly, Ken Kostenbader, Şölen Ekesan, Darrin M. York

Research output: Contribution to journalReview article

Abstract

A predictive understanding of the mechanisms of RNA cleavage is important for the design of emerging technology built from biological and synthetic molecules that have promise for new biochemical and medicinal applications. Over the past 15 years, RNA cleavage reactions involving 2′-O-transphosphorylation have been discussed using a simplified framework introduced by Breaker that consists of four fundamental catalytic strategies (designated α, β, γ, and δ) that contribute to rate enhancement. As more detailed mechanistic data emerge, there is need for the framework to evolve and keep pace. We develop an ontology for discussion of strategies of enzymes that catalyze RNA cleavage via 2′-O-transphosphorylation that stratifies Breaker's framework into primary (1°), secondary (2°), and tertiary (3°) contributions to enable more precise interpretation of mechanism in the context of structure and bonding. Further, we point out instances where atomic-level changes give rise to changes in more than one catalytic contribution, a phenomenon we refer to as "functional blurring". We hope that this ontology will help clarify our conversations and pave the path forward toward a consensus view of these fundamental and fascinating mechanisms. The insight gained will deepen our understanding of RNA cleavage reactions catalyzed by natural protein and RNA enzymes, as well as aid in the design of new engineered DNA and synthetic enzymes.

Original languageEnglish (US)
Pages (from-to)1068-1076
Number of pages9
JournalACS chemical biology
Volume14
Issue number6
DOIs
StatePublished - Jun 21 2019

Fingerprint

RNA Cleavage
Catalytic RNA
Ontology
RNA
Enzymes
Technology
DNA
Molecules
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

Cite this

Bevilacqua, P. C., Harris, M. E., Piccirilli, J. A., Gaines, C., Ganguly, A., Kostenbader, K., ... York, D. M. (2019). An Ontology for Facilitating Discussion of Catalytic Strategies of RNA-Cleaving Enzymes. ACS chemical biology, 14(6), 1068-1076. https://doi.org/10.1021/acschembio.9b00202
Bevilacqua, Philip C. ; Harris, Michael E. ; Piccirilli, Joseph A. ; Gaines, Colin ; Ganguly, Abir ; Kostenbader, Ken ; Ekesan, Şölen ; York, Darrin M. / An Ontology for Facilitating Discussion of Catalytic Strategies of RNA-Cleaving Enzymes. In: ACS chemical biology. 2019 ; Vol. 14, No. 6. pp. 1068-1076.
@article{8f2eb62492bf4ffab0be49d80d95175b,
title = "An Ontology for Facilitating Discussion of Catalytic Strategies of RNA-Cleaving Enzymes",
abstract = "A predictive understanding of the mechanisms of RNA cleavage is important for the design of emerging technology built from biological and synthetic molecules that have promise for new biochemical and medicinal applications. Over the past 15 years, RNA cleavage reactions involving 2′-O-transphosphorylation have been discussed using a simplified framework introduced by Breaker that consists of four fundamental catalytic strategies (designated α, β, γ, and δ) that contribute to rate enhancement. As more detailed mechanistic data emerge, there is need for the framework to evolve and keep pace. We develop an ontology for discussion of strategies of enzymes that catalyze RNA cleavage via 2′-O-transphosphorylation that stratifies Breaker's framework into primary (1°), secondary (2°), and tertiary (3°) contributions to enable more precise interpretation of mechanism in the context of structure and bonding. Further, we point out instances where atomic-level changes give rise to changes in more than one catalytic contribution, a phenomenon we refer to as {"}functional blurring{"}. We hope that this ontology will help clarify our conversations and pave the path forward toward a consensus view of these fundamental and fascinating mechanisms. The insight gained will deepen our understanding of RNA cleavage reactions catalyzed by natural protein and RNA enzymes, as well as aid in the design of new engineered DNA and synthetic enzymes.",
author = "Bevilacqua, {Philip C.} and Harris, {Michael E.} and Piccirilli, {Joseph A.} and Colin Gaines and Abir Ganguly and Ken Kostenbader and Ş{\"o}len Ekesan and York, {Darrin M.}",
year = "2019",
month = "6",
day = "21",
doi = "10.1021/acschembio.9b00202",
language = "English (US)",
volume = "14",
pages = "1068--1076",
journal = "ACS Chemical Biology",
issn = "1554-8929",
publisher = "American Chemical Society",
number = "6",

}

Bevilacqua, PC, Harris, ME, Piccirilli, JA, Gaines, C, Ganguly, A, Kostenbader, K, Ekesan, Ş & York, DM 2019, 'An Ontology for Facilitating Discussion of Catalytic Strategies of RNA-Cleaving Enzymes', ACS chemical biology, vol. 14, no. 6, pp. 1068-1076. https://doi.org/10.1021/acschembio.9b00202

An Ontology for Facilitating Discussion of Catalytic Strategies of RNA-Cleaving Enzymes. / Bevilacqua, Philip C.; Harris, Michael E.; Piccirilli, Joseph A.; Gaines, Colin; Ganguly, Abir; Kostenbader, Ken; Ekesan, Şölen; York, Darrin M.

In: ACS chemical biology, Vol. 14, No. 6, 21.06.2019, p. 1068-1076.

Research output: Contribution to journalReview article

TY - JOUR

T1 - An Ontology for Facilitating Discussion of Catalytic Strategies of RNA-Cleaving Enzymes

AU - Bevilacqua, Philip C.

AU - Harris, Michael E.

AU - Piccirilli, Joseph A.

AU - Gaines, Colin

AU - Ganguly, Abir

AU - Kostenbader, Ken

AU - Ekesan, Şölen

AU - York, Darrin M.

PY - 2019/6/21

Y1 - 2019/6/21

N2 - A predictive understanding of the mechanisms of RNA cleavage is important for the design of emerging technology built from biological and synthetic molecules that have promise for new biochemical and medicinal applications. Over the past 15 years, RNA cleavage reactions involving 2′-O-transphosphorylation have been discussed using a simplified framework introduced by Breaker that consists of four fundamental catalytic strategies (designated α, β, γ, and δ) that contribute to rate enhancement. As more detailed mechanistic data emerge, there is need for the framework to evolve and keep pace. We develop an ontology for discussion of strategies of enzymes that catalyze RNA cleavage via 2′-O-transphosphorylation that stratifies Breaker's framework into primary (1°), secondary (2°), and tertiary (3°) contributions to enable more precise interpretation of mechanism in the context of structure and bonding. Further, we point out instances where atomic-level changes give rise to changes in more than one catalytic contribution, a phenomenon we refer to as "functional blurring". We hope that this ontology will help clarify our conversations and pave the path forward toward a consensus view of these fundamental and fascinating mechanisms. The insight gained will deepen our understanding of RNA cleavage reactions catalyzed by natural protein and RNA enzymes, as well as aid in the design of new engineered DNA and synthetic enzymes.

AB - A predictive understanding of the mechanisms of RNA cleavage is important for the design of emerging technology built from biological and synthetic molecules that have promise for new biochemical and medicinal applications. Over the past 15 years, RNA cleavage reactions involving 2′-O-transphosphorylation have been discussed using a simplified framework introduced by Breaker that consists of four fundamental catalytic strategies (designated α, β, γ, and δ) that contribute to rate enhancement. As more detailed mechanistic data emerge, there is need for the framework to evolve and keep pace. We develop an ontology for discussion of strategies of enzymes that catalyze RNA cleavage via 2′-O-transphosphorylation that stratifies Breaker's framework into primary (1°), secondary (2°), and tertiary (3°) contributions to enable more precise interpretation of mechanism in the context of structure and bonding. Further, we point out instances where atomic-level changes give rise to changes in more than one catalytic contribution, a phenomenon we refer to as "functional blurring". We hope that this ontology will help clarify our conversations and pave the path forward toward a consensus view of these fundamental and fascinating mechanisms. The insight gained will deepen our understanding of RNA cleavage reactions catalyzed by natural protein and RNA enzymes, as well as aid in the design of new engineered DNA and synthetic enzymes.

UR - http://www.scopus.com/inward/record.url?scp=85067653231&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067653231&partnerID=8YFLogxK

U2 - 10.1021/acschembio.9b00202

DO - 10.1021/acschembio.9b00202

M3 - Review article

C2 - 31095369

AN - SCOPUS:85067653231

VL - 14

SP - 1068

EP - 1076

JO - ACS Chemical Biology

JF - ACS Chemical Biology

SN - 1554-8929

IS - 6

ER -