The Active Site of a Carbohydrate Esterase Displays Divergent Catalytic and Noncatalytic Binding Functions
(2009) In PLoS Biology 7(3). p.687-697- Abstract
- 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... (More)
- 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. (Less)
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https://lup.lub.lu.se/record/1399438
- author
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Biology
- volume
- 7
- issue
- 3
- pages
- 687 - 697
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000265412600024
- pmid:19338387
- scopus:66149093843
- ISSN
- 1545-7885
- DOI
- 10.1371/journal.pbio.1000071
- language
- English
- LU publication?
- yes
- id
- 99bcd47b-4055-4d41-9956-692d1f854ff0 (old id 1399438)
- date added to LUP
- 2016-04-01 13:30:02
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- 2022-01-27 19:30:56
@article{99bcd47b-4055-4d41-9956-692d1f854ff0,
abstract = {{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.}},
author = {{Montanier, Cedric and Money, Victoria A. and Pires, Virginia M. R. and Flint, James E. and Pinheiro, Benedita A. and Goyal, Arun and Prates, Jose A. M. and Izumi, Atsushi and Stålbrand, Henrik and Morland, Carl and Cartmell, Alan and Kolenová, Katarina and Topakas, Evangelos and Dodson, Eleanor J. and Bolam, David N. and Davies, Gideon J. and Fontes, Carlos M. G. A. and Gilbert, Harry J.}},
issn = {{1545-7885}},
language = {{eng}},
number = {{3}},
pages = {{687--697}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Biology}},
title = {{The Active Site of a Carbohydrate Esterase Displays Divergent Catalytic and Noncatalytic Binding Functions}},
url = {{http://dx.doi.org/10.1371/journal.pbio.1000071}},
doi = {{10.1371/journal.pbio.1000071}},
volume = {{7}},
year = {{2009}},
}