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Exploring Enzyme Evolution from Changes in Sequence, Structure, and Function

Tyzack, JD; Furnham, N; Sillitoe, I; Orengo, CM; Thornton, JM; (2019) Exploring Enzyme Evolution from Changes in Sequence, Structure, and Function. Methods in Molecular Biology , 1851 pp. 263-275. 10.1007/978-1-4939-8736-8_14. Green open access

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Abstract

The goal of our research is to increase our understanding of how biology works at the molecular level, with a particular focus on how enzymes evolve their functions through adaptations to generate new specificities and mechanisms. FunTree (Sillitoe and Furnham, Nucleic Acids Res 44:D317-D323, 2016) is a resource that brings together sequence, structure, phylogenetic, and chemical and mechanistic information for 2340 CATH superfamilies (Sillitoe et al., Nucleic Acids Res 43:D376-D381, 2015) (which all contain at least one enzyme) to allow evolution to be investigated within a structurally defined superfamily.We will give an overview of FunTree's use of sequence and structural alignments to cluster proteins within a superfamily into structurally similar groups (SSGs) and generate phylogenetic trees augmented by ancestral character estimations (ACE). This core information is supplemented with new measures of functional similarity (Rahman et al., Nat Methods 11:171-174, 2014) to compare enzyme reactions based on overall bond changes, reaction centers (the local environment atoms involved in the reaction), and the structural similarities of the metabolites involved in the reaction. These trees are also decorated with taxonomic and Enzyme Commission (EC) code and GO annotations, forming the basis of a comprehensive web interface that can be found at http://www.funtree.info . In this chapter, we will discuss the various analyses and supporting computational tools in more detail, describing the steps required to extract information.

Type: Article
Title: Exploring Enzyme Evolution from Changes in Sequence, Structure, and Function
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/978-1-4939-8736-8_14
Publisher version: https://doi.org/10.1007/978-1-4939-8736-8_14
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: CATH, EC-Blast, Enzyme evolution, FunTree, Phylogenetic tree
UCL classification: UCL
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: https://discovery.ucl.ac.uk/id/eprint/10070673
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