Functional evolution of PLP-dependent enzymes based on active-site structural similarities

Jonathan Catazaro, Adam Caprez, Ashu Guru, David R Swanson, Robert Powers

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5′-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS.

Original languageEnglish (US)
Pages (from-to)2597-2608
Number of pages12
JournalProteins: Structure, Function and Bioinformatics
Volume82
Issue number10
DOIs
StatePublished - Jan 1 2014

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Pyridoxal Phosphate
Catalytic Domain
Enzymes
Proteins
Substrate Specificity
Software
Databases
Substrates

Keywords

  • CPASS
  • Functional evolution
  • Ligand binding sites
  • PLP-dependent enzymes

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Functional evolution of PLP-dependent enzymes based on active-site structural similarities. / Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David R; Powers, Robert.

In: Proteins: Structure, Function and Bioinformatics, Vol. 82, No. 10, 01.01.2014, p. 2597-2608.

Research output: Contribution to journalArticle

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