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

  • Jonathan D. TyzackEmail author
  • Nicholas Furnham
  • Ian Sillitoe
  • Christine M. Orengo
  • Janet M. Thornton
Part of the Methods in Molecular Biology book series (MIMB, volume 1851)


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 In this chapter, we will discuss the various analyses and supporting computational tools in more detail, describing the steps required to extract information.

Key words

FunTree Enzyme evolution CATH EC-Blast Phylogenetic tree 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jonathan D. Tyzack
    • 1
    Email author
  • Nicholas Furnham
    • 2
  • Ian Sillitoe
    • 3
  • Christine M. Orengo
    • 3
  • Janet M. Thornton
    • 1
  1. 1.EMBL-EBIWellcome Genome Campus, HinxtonCambridgeUK
  2. 2.London School of Hygiene and Tropical MedicineLondonUK
  3. 3.Institute of Structural and Molecular BiologyUniversity College LondonLondonUK

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