Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily

Abstract In this work, we applied the sequence-based statistical coupling analysis approach to characterize conserved amino acid networks important for biochemical function in the pancreatic-type ribonuclease (ptRNase) superfamily. This superfamily-wide analysis indicates a decomposition of the RNas...

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Autores principales:	Chitra Narayanan, Donald Gagné, Kimberly A. Reynolds, Nicolas Doucet
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e1f69c4e9b494b9dbefb82876d0eca19
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spelling	oai:doaj.org-article:e1f69c4e9b494b9dbefb82876d0eca192021-12-02T15:04:54ZConserved amino acid networks modulate discrete functional properties in an enzyme superfamily10.1038/s41598-017-03298-42045-2322https://doaj.org/article/e1f69c4e9b494b9dbefb82876d0eca192017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03298-4https://doaj.org/toc/2045-2322Abstract In this work, we applied the sequence-based statistical coupling analysis approach to characterize conserved amino acid networks important for biochemical function in the pancreatic-type ribonuclease (ptRNase) superfamily. This superfamily-wide analysis indicates a decomposition of the RNase tertiary structure into spatially distributed yet physically connected networks of co-evolving amino acids, termed sectors. Comparison of this statistics-based description with new NMR experiments data shows that discrete amino acid networks, termed sectors, control the tuning of distinct functional properties in different enzyme homologs. Further, experimental characterization of evolutionarily distant sequences reveals that sequence variation at sector positions can distinguish homologs with a conserved dynamic pattern and optimal catalytic activity from those with altered dynamics and diminished catalytic activities. Taken together, these results provide important insights into the mechanistic design of the ptRNase superfamily, and presents a structural basis for evolutionary tuning of function in functionally diverse enzyme homologs.Chitra NarayananDonald GagnéKimberly A. ReynoldsNicolas DoucetNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chitra Narayanan Donald Gagné Kimberly A. Reynolds Nicolas Doucet Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily
description	Abstract In this work, we applied the sequence-based statistical coupling analysis approach to characterize conserved amino acid networks important for biochemical function in the pancreatic-type ribonuclease (ptRNase) superfamily. This superfamily-wide analysis indicates a decomposition of the RNase tertiary structure into spatially distributed yet physically connected networks of co-evolving amino acids, termed sectors. Comparison of this statistics-based description with new NMR experiments data shows that discrete amino acid networks, termed sectors, control the tuning of distinct functional properties in different enzyme homologs. Further, experimental characterization of evolutionarily distant sequences reveals that sequence variation at sector positions can distinguish homologs with a conserved dynamic pattern and optimal catalytic activity from those with altered dynamics and diminished catalytic activities. Taken together, these results provide important insights into the mechanistic design of the ptRNase superfamily, and presents a structural basis for evolutionary tuning of function in functionally diverse enzyme homologs.
format	article
author	Chitra Narayanan Donald Gagné Kimberly A. Reynolds Nicolas Doucet
author_facet	Chitra Narayanan Donald Gagné Kimberly A. Reynolds Nicolas Doucet
author_sort	Chitra Narayanan
title	Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily
title_short	Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily
title_full	Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily
title_fullStr	Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily
title_full_unstemmed	Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily
title_sort	conserved amino acid networks modulate discrete functional properties in an enzyme superfamily
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e1f69c4e9b494b9dbefb82876d0eca19
work_keys_str_mv	AT chitranarayanan conservedaminoacidnetworksmodulatediscretefunctionalpropertiesinanenzymesuperfamily AT donaldgagne conservedaminoacidnetworksmodulatediscretefunctionalpropertiesinanenzymesuperfamily AT kimberlyareynolds conservedaminoacidnetworksmodulatediscretefunctionalpropertiesinanenzymesuperfamily AT nicolasdoucet conservedaminoacidnetworksmodulatediscretefunctionalpropertiesinanenzymesuperfamily
_version_	1718389049350160384

Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily

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