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Promiscuity comes at a price: Catalytic versatility vs efficiency in different metal ion derivatives of the potential bioremediator GpdQ

Daumann, Lena J; McCarthy, Bianca Y; Hadler, Kieran S; Murray, Tracy; Gahan, Lawrence; Larrabee, James A; Ollis, David; Schenk, Gerhard

Description

The glycerophosphodiesterase from Enterobacter aerogenes (GpdQ) is a highly promiscuous dinuclear metallohydrolase with respect to both substrate specificity and metal ion composition. While this promiscuity may adversely affect the enzyme's catalytic efficiency its ability to hydrolyse some organophosphates (OPs) and by-products of OP degradation have turned GpdQ into a promising candidate for bioremedial applications. Here, we investigated both metal ion binding and the effect of the metal...[Show more]

dc.contributor.authorDaumann, Lena J
dc.contributor.authorMcCarthy, Bianca Y
dc.contributor.authorHadler, Kieran S
dc.contributor.authorMurray, Tracy
dc.contributor.authorGahan, Lawrence
dc.contributor.authorLarrabee, James A
dc.contributor.authorOllis, David
dc.contributor.authorSchenk, Gerhard
dc.date.accessioned2015-12-10T23:35:28Z
dc.identifier.issn1570-9639
dc.identifier.urihttp://hdl.handle.net/1885/69862
dc.description.abstractThe glycerophosphodiesterase from Enterobacter aerogenes (GpdQ) is a highly promiscuous dinuclear metallohydrolase with respect to both substrate specificity and metal ion composition. While this promiscuity may adversely affect the enzyme's catalytic efficiency its ability to hydrolyse some organophosphates (OPs) and by-products of OP degradation have turned GpdQ into a promising candidate for bioremedial applications. Here, we investigated both metal ion binding and the effect of the metal ion composition on catalysis. The prevalent in vivo metal ion composition for GpdQ is proposed to be of the type Fe(II)Zn(II), a reflection of natural abundance rather than catalytic optimisation. The Fe(II) appears to have lower binding affinity than other divalent metal ions, and the catalytic efficiency of this mixed metal center is considerably smaller than that of Mn(II), Co(II) or Cd(II)-containing derivatives of GpdQ. Interestingly, metal ion replacements do not only affect catalytic efficiency but also the optimal pH range for the reaction, suggesting that different metal ion combinations may employ different mechanistic strategies. These metal ion-triggered modulations are likely to be mediated via an extensive hydrogen bond network that links the two metal ion binding sites via residues in the substrate binding pocket. The observed functional diversity may be the cause for the modest catalytic efficiency of wild-type GpdQ but may also be essential to enable the enzyme to evolve rapidly to alter substrate specificity and enhance kcat values, as has recently been demonstrated in a directed evolution experiment. This article is part of a Special Issue entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.
dc.publisherElsevier
dc.sourceBiochimica et Biophysica Acta: Proteins & Proteomics
dc.subjectKeywords: bacterial enzyme; cadmium; cobalt; divalent cation; esterase; glycerophosphodiesterase; manganese; metal ion; unclassified drug; article; binding site; bioremediation; catalysis; Enterobacter aerogenes; enzyme specificity; enzyme substrate; helium cadmium Binuclear metallohydrolases; Bioremediation; Glycerophosphodiesterase; Metal ion replacement; Reaction mechanism
dc.titlePromiscuity comes at a price: Catalytic versatility vs efficiency in different metal ion derivatives of the potential bioremediator GpdQ
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume1834
dc.date.issued2013
local.identifier.absfor030499 - Medicinal and Biomolecular Chemistry not elsewhere classified
local.identifier.ariespublicationf5625xPUB2143
local.type.statusPublished Version
local.contributor.affiliationDaumann, Lena J, University of Queensland
local.contributor.affiliationMcCarthy, Bianca Y, University of Queensland
local.contributor.affiliationHadler, Kieran S, University of Queensland
local.contributor.affiliationMurray, Tracy, College of Physical and Mathematical Sciences, ANU
local.contributor.affiliationGahan, Lawrence, University of Queensland
local.contributor.affiliationLarrabee, James A, Middlebury College
local.contributor.affiliationOllis, David, College of Physical and Mathematical Sciences, ANU
local.contributor.affiliationSchenk, Gerhard, University of Queensland
local.description.embargo2037-12-31
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage425
local.bibliographicCitation.lastpage432
local.identifier.doi10.1016/j.bbapap.2012.02.004
local.identifier.absseo970103 - Expanding Knowledge in the Chemical Sciences
dc.date.updated2016-02-24T08:55:04Z
local.identifier.scopusID2-s2.0-84871711835
local.identifier.thomsonID000314620400045
CollectionsANU Research Publications

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