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Evolved, Selective Erasers of Distinct Lysine Acylations

Lysine acylations, a family of diverse protein modifications varying in acyl‐group length, charge, and saturation, are linked to many important physiological processes. Only a small set of substrate‐promiscuous lysine acetyltransferases and deacetylases (KDACs) install and remove this vast variety o...

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Autores principales: Spinck, Martin, Neumann‐Staubitz, Petra, Ecke, Maria, Gasper, Raphael, Neumann, Heinz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317389/
https://www.ncbi.nlm.nih.gov/pubmed/32187803
http://dx.doi.org/10.1002/anie.202002899
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author Spinck, Martin
Neumann‐Staubitz, Petra
Ecke, Maria
Gasper, Raphael
Neumann, Heinz
author_facet Spinck, Martin
Neumann‐Staubitz, Petra
Ecke, Maria
Gasper, Raphael
Neumann, Heinz
author_sort Spinck, Martin
collection PubMed
description Lysine acylations, a family of diverse protein modifications varying in acyl‐group length, charge, and saturation, are linked to many important physiological processes. Only a small set of substrate‐promiscuous lysine acetyltransferases and deacetylases (KDACs) install and remove this vast variety of modifications. Engineered KDACs that remove only one type of acylation would help to dissect the different contributions of distinct acylations. We developed a bacterial selection system for the directed evolution of KDACs and identified variants up to 400 times more selective for butyryl‐lysine compared to crotonyl‐lysine. Structural analyses revealed that the enzyme adopts different conformational states depending on the type of acylation of the bound peptide. We used the butyryl‐selective KDAC variant to shift the cellular acylation spectrum towards increased lysine crotonylation. These new enzymes will help in dissecting the roles of different lysine acylations in cell physiology.
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spelling pubmed-73173892020-06-30 Evolved, Selective Erasers of Distinct Lysine Acylations Spinck, Martin Neumann‐Staubitz, Petra Ecke, Maria Gasper, Raphael Neumann, Heinz Angew Chem Int Ed Engl Research Articles Lysine acylations, a family of diverse protein modifications varying in acyl‐group length, charge, and saturation, are linked to many important physiological processes. Only a small set of substrate‐promiscuous lysine acetyltransferases and deacetylases (KDACs) install and remove this vast variety of modifications. Engineered KDACs that remove only one type of acylation would help to dissect the different contributions of distinct acylations. We developed a bacterial selection system for the directed evolution of KDACs and identified variants up to 400 times more selective for butyryl‐lysine compared to crotonyl‐lysine. Structural analyses revealed that the enzyme adopts different conformational states depending on the type of acylation of the bound peptide. We used the butyryl‐selective KDAC variant to shift the cellular acylation spectrum towards increased lysine crotonylation. These new enzymes will help in dissecting the roles of different lysine acylations in cell physiology. John Wiley and Sons Inc. 2020-04-24 2020-06-26 /pmc/articles/PMC7317389/ /pubmed/32187803 http://dx.doi.org/10.1002/anie.202002899 Text en © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Spinck, Martin
Neumann‐Staubitz, Petra
Ecke, Maria
Gasper, Raphael
Neumann, Heinz
Evolved, Selective Erasers of Distinct Lysine Acylations
title Evolved, Selective Erasers of Distinct Lysine Acylations
title_full Evolved, Selective Erasers of Distinct Lysine Acylations
title_fullStr Evolved, Selective Erasers of Distinct Lysine Acylations
title_full_unstemmed Evolved, Selective Erasers of Distinct Lysine Acylations
title_short Evolved, Selective Erasers of Distinct Lysine Acylations
title_sort evolved, selective erasers of distinct lysine acylations
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317389/
https://www.ncbi.nlm.nih.gov/pubmed/32187803
http://dx.doi.org/10.1002/anie.202002899
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