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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3387218?pdf=render |
| _version_ | 1818437568703758336 |
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| author | Sajid Noor Matthew C Taylor Robyn J Russell Lars S Jermiin Colin J Jackson John G Oakeshott Colin Scott |
| author_facet | Sajid Noor Matthew C Taylor Robyn J Russell Lars S Jermiin Colin J Jackson John G Oakeshott Colin Scott |
| author_sort | Sajid Noor |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T17:26:45Z |
| format | Article |
| id | doaj.art-1fae93dadbcb454cb61b8261544c90b3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T17:26:45Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1fae93dadbcb454cb61b8261544c90b32022-12-21T22:53:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3982210.1371/journal.pone.0039822Intramolecular epistasis and the evolution of a new enzymatic function.Sajid NoorMatthew C TaylorRobyn J RussellLars S JermiinColin J JacksonJohn G OakeshottColin ScottAtrazine 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.http://europepmc.org/articles/PMC3387218?pdf=render |
| spellingShingle | Sajid Noor Matthew C Taylor Robyn J Russell Lars S Jermiin Colin J Jackson John G Oakeshott Colin Scott Intramolecular epistasis and the evolution of a new enzymatic function. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3387218?pdf=render |
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