Identification of functional subclasses in the DJ-1 superfamily proteins

Ying Wei, Dagmar Ringe, Mark A Wilson, Mary Jo Ondrechen

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Genomics has posed the challenge of determination of protein function from sequence and/or 3-D structure. Functional assignment from sequence relationships can be misleading, and structural similarity does not necessarily imply functional similarity. Proteins in the DJ-1 family, many of which are of unknown function, are examples of proteins with both sequence and fold similarity that span multiple functional classes. THEMATICS (theoretical microscopic titration curves), an electrostatics-based computational approach to functional site prediction, is used to sort proteins in the DJ-1 family into different functional classes. Active site residues are predicted for the eight distinct DJ-1 proteins with available 3-D structures. Placement of the predicted residues onto a structural alignment for six of these proteins reveals three distinct types of active sites. Each type overlaps only partially with the others, with only one residue in common across all six sets of predicted residues. Human DJ-1 and YajL from Escherichia coli have very similar predicted active sites and belong to the same probable functional group. Protease I, a known cysteine protease from Pyrococcus horikoshii, and PfpI/YhbO from E. coli, a hypothetical protein of unknown function, belong to a separate class. THEMATICS predicts a set of residues that is typical of a cysteine protease for Protease I; the prediction for PfpI/YhbO bears some similarity. YDR533Cp from Saccharomyces cerevisiae, of unknown function, and the known chaperone Hsp31 from E. coli constitute a third group with nearly identical predicted active sites. While the first four proteins have predicted active sites at dimer interfaces, YDR533Cp and Hsp31 both have predicted sites contained within each subunit. Although YDR533Cp and Hsp31 form different dimers with different orientations between the subunits, the predicted active sites are superimposable within the monomer structures. Thus, the three predicted functional classes form four different types of quaternary structures. The computational prediction of the functional sites for protein structures of unknown function provides valuable clues for functional classification.

Original languageEnglish (US)
Pages (from-to)120-126
Number of pages7
JournalPLoS Computational Biology
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2007

Fingerprint

Catalytic Domain
active sites
Proteins
Protein
protein
Protease
Cysteine Proteases
proteins
Escherichia Coli
Escherichia coli
Unknown
cysteine proteinases
Pyrococcus horikoshii
Peptide Hydrolases
Dimer
titration
3D
prediction
Titration
Prediction

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this

Identification of functional subclasses in the DJ-1 superfamily proteins. / Wei, Ying; Ringe, Dagmar; Wilson, Mark A; Ondrechen, Mary Jo.

In: PLoS Computational Biology, Vol. 3, No. 1, 01.01.2007, p. 120-126.

Research output: Contribution to journalArticle

Wei, Ying ; Ringe, Dagmar ; Wilson, Mark A ; Ondrechen, Mary Jo. / Identification of functional subclasses in the DJ-1 superfamily proteins. In: PLoS Computational Biology. 2007 ; Vol. 3, No. 1. pp. 120-126.
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