Functional Evolution of Proteins

Jonathan Catazaro, Adam Caprez, David Swanson, Robert Powers

Research output: Contribution to journalArticle

Abstract

The functional evolution of proteins advances through gene duplication followed by functional drift, whereas molecular evolution occurs through random mutational events. Over time, protein active-site structures or functional epitopes remain highly conserved, which enables relationships to be inferred between distant orthologs or paralogs. In this study, we present the first functional clustering and evolutionary analysis of the RCSB Protein Data Bank (RCSB PDB) based on similarities between active-site structures. All of the ligand-bound proteins within the RCSB PDB were scored using our Comparison of Protein Active-site Structures (CPASS) software and database (http://cpass.unl.edu/). Principal component analysis was then used to identify 4431 representative structures to construct a phylogenetic tree based on the CPASS comparative scores (http://itol.embl.de/shared/jcatazaro). The resulting phylogenetic tree identified a sequential, step-wise evolution of protein active-sites and provides novel insights into the emergence of protein function or changes in substrate specificity based on subtle changes in geometry and amino acid composition.

Original languageEnglish (US)
Pages (from-to)492-501
Number of pages10
JournalProteins: Structure, Function and Bioinformatics
Volume87
Issue number6
DOIs
StatePublished - Jun 2019

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Catalytic Domain
Proteins
Databases
Gene Duplication
Molecular Evolution
Substrate Specificity
Principal Component Analysis
Principal component analysis
Cluster Analysis
Epitopes
Software
Genes
Ligands
Amino Acids
Geometry
Substrates
Chemical analysis

Keywords

  • CPASS
  • functional evolution
  • protein active-sites
  • proteins

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Functional Evolution of Proteins. / Catazaro, Jonathan; Caprez, Adam; Swanson, David; Powers, Robert.

In: Proteins: Structure, Function and Bioinformatics, Vol. 87, No. 6, 06.2019, p. 492-501.

Research output: Contribution to journalArticle

Catazaro, Jonathan ; Caprez, Adam ; Swanson, David ; Powers, Robert. / Functional Evolution of Proteins. In: Proteins: Structure, Function and Bioinformatics. 2019 ; Vol. 87, No. 6. pp. 492-501.
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