Cargando…
Intramolecular Epistasis and the Evolution of a New Enzymatic Function
Atrazine chlorohydrolase (AtzA) and its close relative melamine deaminase (TriA) differ by just nine amino acid substitutions but have distinct catalytic activities. Together, they offer an informative model system to study the molecular processes that underpin the emergence of new enzymatic functio...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387218/ https://www.ncbi.nlm.nih.gov/pubmed/22768133 http://dx.doi.org/10.1371/journal.pone.0039822 |
_version_ | 1782237077372403712 |
---|---|
author | Noor, Sajid Taylor, Matthew C. Russell, Robyn J. Jermiin, Lars S. Jackson, Colin J. Oakeshott, John G. Scott, Colin |
author_facet | Noor, Sajid Taylor, Matthew C. Russell, Robyn J. Jermiin, Lars S. Jackson, Colin J. Oakeshott, John G. Scott, Colin |
author_sort | Noor, Sajid |
collection | PubMed |
description | Atrazine chlorohydrolase (AtzA) and its close relative melamine deaminase (TriA) differ by just nine amino acid substitutions but have distinct catalytic activities. Together, they offer an informative model system to study the molecular processes that underpin the emergence of new enzymatic function. Here we have constructed the potential evolutionary trajectories between AtzA and TriA, and characterized the catalytic activities and biophysical properties of the intermediates along those trajectories. The order in which the nine amino acid substitutions that separate the enzymes could be introduced to either enzyme, while maintaining significant catalytic activity, was dictated by epistatic interactions, principally between three amino acids within the active site: namely, S331C, N328D and F84L. The mechanistic basis for the epistatic relationships is consistent with a model for the catalytic mechanisms in which protonation is required for hydrolysis of melamine, but not atrazine. |
format | Online Article Text |
id | pubmed-3387218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33872182012-07-05 Intramolecular Epistasis and the Evolution of a New Enzymatic Function Noor, Sajid Taylor, Matthew C. Russell, Robyn J. Jermiin, Lars S. Jackson, Colin J. Oakeshott, John G. Scott, Colin PLoS One Research Article Atrazine chlorohydrolase (AtzA) and its close relative melamine deaminase (TriA) differ by just nine amino acid substitutions but have distinct catalytic activities. Together, they offer an informative model system to study the molecular processes that underpin the emergence of new enzymatic function. Here we have constructed the potential evolutionary trajectories between AtzA and TriA, and characterized the catalytic activities and biophysical properties of the intermediates along those trajectories. The order in which the nine amino acid substitutions that separate the enzymes could be introduced to either enzyme, while maintaining significant catalytic activity, was dictated by epistatic interactions, principally between three amino acids within the active site: namely, S331C, N328D and F84L. The mechanistic basis for the epistatic relationships is consistent with a model for the catalytic mechanisms in which protonation is required for hydrolysis of melamine, but not atrazine. Public Library of Science 2012-06-29 /pmc/articles/PMC3387218/ /pubmed/22768133 http://dx.doi.org/10.1371/journal.pone.0039822 Text en Noor et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Noor, Sajid Taylor, Matthew C. Russell, Robyn J. Jermiin, Lars S. Jackson, Colin J. Oakeshott, John G. Scott, Colin Intramolecular Epistasis and the Evolution of a New Enzymatic Function |
title | Intramolecular Epistasis and the Evolution of a New Enzymatic Function |
title_full | Intramolecular Epistasis and the Evolution of a New Enzymatic Function |
title_fullStr | Intramolecular Epistasis and the Evolution of a New Enzymatic Function |
title_full_unstemmed | Intramolecular Epistasis and the Evolution of a New Enzymatic Function |
title_short | Intramolecular Epistasis and the Evolution of a New Enzymatic Function |
title_sort | intramolecular epistasis and the evolution of a new enzymatic function |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387218/ https://www.ncbi.nlm.nih.gov/pubmed/22768133 http://dx.doi.org/10.1371/journal.pone.0039822 |
work_keys_str_mv | AT noorsajid intramolecularepistasisandtheevolutionofanewenzymaticfunction AT taylormatthewc intramolecularepistasisandtheevolutionofanewenzymaticfunction AT russellrobynj intramolecularepistasisandtheevolutionofanewenzymaticfunction AT jermiinlarss intramolecularepistasisandtheevolutionofanewenzymaticfunction AT jacksoncolinj intramolecularepistasisandtheevolutionofanewenzymaticfunction AT oakeshottjohng intramolecularepistasisandtheevolutionofanewenzymaticfunction AT scottcolin intramolecularepistasisandtheevolutionofanewenzymaticfunction |