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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 Graham; Scott, Colin

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...[Show more]

dc.contributor.authorNoor, Sajid
dc.contributor.authorTaylor, Matthew C
dc.contributor.authorRussell, Robyn J
dc.contributor.authorJermiin, Lars S
dc.contributor.authorJackson, Colin J
dc.contributor.authorOakeshott, John Graham
dc.contributor.authorScott, Colin
dc.date.accessioned2015-10-27T23:17:25Z
dc.date.available2015-10-27T23:17:25Z
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1885/16127
dc.description.abstractAtrazine 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.
dc.description.sponsorshipSN was supported by an Australian National University Postgraduate Scholarship and CSIRO’s Synthetic Enzymes Emerging Science Initiative.
dc.format11 pages
dc.publisherPublic Library of Science
dc.rights© 2012 Noor et al. 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 credited.
dc.sourcePLoS ONE
dc.subjectamino acid substitution
dc.subjectamino acids
dc.subjectaminohydrolases
dc.subjectcatalytic domain
dc.subjectenzyme stability
dc.subjecthydrolases
dc.subjectkinetics
dc.subjectmodels, molecular
dc.subjectpseudomonas
dc.subjecttransition temperature
dc.subjectepistasis, genetic
dc.subjectevolution, molecular
dc.titleIntramolecular epistasis and the evolution of a new enzymatic function
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume7
dcterms.dateAccepted2012-05-28
dc.date.issued2012-06-29
local.identifier.absfor030503
local.identifier.ariespublicationu4005981xPUB624
local.publisher.urlhttps://www.plos.org/
local.type.statusPublished Version
local.contributor.affiliationNoor, Sajid, College of Physical and Mathematical Sciences, CPMS Research School of Chemistry, RSC General, The Australian National University
local.contributor.affiliationTaylor, Matthew C, CSIRO Ecosystem Sciences, Australia
local.contributor.affiliationRussell, Robyn J, CSIRO Ecosystem Sciences, Australia
local.contributor.affiliationJermiin, Lars S, CSIRO Ecosystem Sciences, Australia
local.contributor.affiliationJackson, Colin, College of Physical and Mathematical Sciences, CPMS Research School of Chemistry, RSC General, The Australian National University
local.contributor.affiliationOakeshott , John, CSIRO Ecosystems Science, Australia
local.contributor.affiliationScott, Colin, CSIRO Ecosystem Sciences, Australia
local.identifier.essn1932-6203
local.bibliographicCitation.issue6
local.bibliographicCitation.startpagee39822
local.bibliographicCitation.lastpage11
local.identifier.doi10.1371/journal.pone.0039822
local.identifier.absseo970103
dc.date.updated2015-12-10T08:26:06Z
local.identifier.scopusID2-s2.0-84863090430
local.identifier.thomsonID000305892100103
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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