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Exploring the evolution of novel enzyme functions within structurally defined protein superfamilies.

Furnham, N; Sillitoe, I; Holliday, GL; Cuff, AL; Laskowski, RA; Orengo, CA; Thornton, JM; (2012) Exploring the evolution of novel enzyme functions within structurally defined protein superfamilies. PLoS Comput Biol , 8 (3) , Article e1002403. 10.1371/journal.pcbi.1002403. Green open access

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Abstract

In order to understand the evolution of enzyme reactions and to gain an overview of biological catalysis we have combined sequence and structural data to generate phylogenetic trees in an analysis of 276 structurally defined enzyme superfamilies, and used these to study how enzyme functions have evolved. We describe in detail the analysis of two superfamilies to illustrate different paradigms of enzyme evolution. Gathering together data from all the superfamilies supports and develops the observation that they have all evolved to act on a diverse set of substrates, whilst the evolution of new chemistry is much less common. Despite that, by bringing together so much data, we can provide a comprehensive overview of the most common and rare types of changes in function. Our analysis demonstrates on a larger scale than previously studied, that modifications in overall chemistry still occur, with all possible changes at the primary level of the Enzyme Commission (E.C.) classification observed to a greater or lesser extent. The phylogenetic trees map out the evolutionary route taken within a superfamily, as well as all the possible changes within a superfamily. This has been used to generate a matrix of observed exchanges from one enzyme function to another, revealing the scale and nature of enzyme evolution and that some types of exchanges between and within E.C. classes are more prevalent than others. Surprisingly a large proportion (71%) of all known enzyme functions are performed by this relatively small set of 276 superfamilies. This reinforces the hypothesis that relatively few ancient enzymatic domain superfamilies were progenitors for most of the chemistry required for life.

Type: Article
Title: Exploring the evolution of novel enzyme functions within structurally defined protein superfamilies.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pcbi.1002403
Publisher version: http://dx.doi.org/10.1371/journal.pcbi.1002403
Language: English
Additional information: © 2012 Furnham 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. Funding: NF and IS are funded by the Wellcome Trust (www.wellcome.ac.uk) (Grant No. 081989/Z/07/A). ALC is funded by the BBSRC (www.bbsrc.ac.uk) and GLH is funded by EMBL (www.embl.org/). RAL is funded in part by US Department of Energy (www.energy.gov) Contract DE-AC02-06CH11357 as part of the Midwest Center For Structural Genomics (www.mcsg.anl.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Amino Acid Sequence, Enzymes, Evolution, Molecular, Molecular Sequence Data, Sequence Analysis, Protein, Structure-Activity Relationship
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1380539
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