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The Active Site of ...
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Montanier, Cedric
(author)
The Active Site of a Carbohydrate Esterase Displays Divergent Catalytic and Noncatalytic Binding Functions
- Article/chapterEnglish2009
Publisher, publication year, extent ...
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2009-03-31
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Public Library of Science (PLoS),2009
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:99bcd47b-4055-4d41-9956-692d1f854ff0
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https://lup.lub.lu.se/record/1399438URI
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https://doi.org/10.1371/journal.pbio.1000071DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Multifunctional proteins, which play a critical role in many biological processes, have typically evolved through the recruitment of different domains that have the required functional diversity. Thus the different activities displayed by these proteins are mediated by spatially distinct domains, consistent with the specific chemical requirements of each activity. Indeed, current evolutionary theory argues that the colocalization of diverse activities within an enzyme is likely to be a rare event, because it would compromise the existing activity of the protein. In contrast to this view, a potential example of multifunctional recruitment into a single protein domain is provided by CtCel5C-CE2, which contains an N-terminal module that displays cellulase activity and a C-terminal module, CtCE2, which exhibits a noncatalytic cellulose-binding function but also shares sequence identity with the CE2 family of esterases. Here we show that, unlike other CE2 members, the CtCE2 domain displays divergent catalytic esterase and noncatalytic carbohydrate binding functions. Intriguingly, these diverse activities are housed within the same site on the protein. Thus, a critical component of the active site of CtCE2, the catalytic Ser-His dyad, in harness with inserted aromatic residues, confers noncatalytic binding to cellulose whilst the active site of the domain retains its esterase activity. CtCE2 catalyses deacetylation of noncellulosic plant structural polysaccharides to deprotect these substrates for attack by other enzymes. Yet it also acts as a cellulose-binding domain, which promotes the activity of the appended cellulase on recalcitrant substrates. The CE2 family encapsulates the requirement for multiple activities by biocatalysts that attack challenging macromolecular substrates, including the grafting of a second, powerful and discrete noncatalytic binding functionality into the active site of an enzyme. This article provides a rare example of "gene sharing,'' where the introduction of a second functionality into the active site of an enzyme does not compromise the original activity of the biocatalyst.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Money, Victoria A.
(author)
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Pires, Virginia M. R.
(author)
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Flint, James E.
(author)
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Pinheiro, Benedita A.
(author)
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Goyal, Arun
(author)
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Prates, Jose A. M.
(author)
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Izumi, Atsushi
(author)
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Stålbrand, HenrikLund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)biok-hst
(author)
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Morland, Carl
(author)
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Cartmell, Alan
(author)
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Kolenová, KatarinaLund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)bioc-ktk
(author)
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Topakas, Evangelos
(author)
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Dodson, Eleanor J.
(author)
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Bolam, David N.
(author)
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Davies, Gideon J.
(author)
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Fontes, Carlos M. G. A.
(author)
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Gilbert, Harry J.
(author)
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Biokemi och StrukturbiologiCentrum för Molekylär Proteinvetenskap
(creator_code:org_t)
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In:PLoS Biology: Public Library of Science (PLoS)7:3, s. 687-6971545-7885
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Flint, James E.
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Prates, Jose A. ...
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Izumi, Atsushi
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Morland, Carl
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Kolenová, Katari ...
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Topakas, Evangel ...
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Dodson, Eleanor ...
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Davies, Gideon J ...
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Fontes, Carlos M ...
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Gilbert, Harry J ...
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