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Enzymes in quest of function

Enzymes en quête de fonction
Published on 22 June 2018

Proteins in quest of function

Contacts : Marcel Salanoubat, Karine Bastard

Researchers from CEA-Gensocope-UMR « Genomics Metabolics » propose an innovative method for elucidating the hitherto enigmatic functions of proteins. The study was published on line in the journal Nature Chemical Biology on 17 November.

The work is a response to the very general issue of the gulf opening up between the discovery of proteins by new sequencing technologies, the number of which is growing exponentially, and their functions which are only slowly being determined. The complexity may be reduced by grouping the proteins in families to which functions are allocated on the basis of annotation of a few of the members. But the function of certain families remains mysterious. However, they represent an important potential for new functions and are worthy of special interest.

In order to further elucidate the families, the researchers use contextual and structural information together with experimental analyses. Prior work on the fermentation of lysine oriented the choice of a family of proteins of unknown function (DUF849). The team first identified the function of one of the members and determined its reaction mechanism by analysis of its 3-dimensional structure. The approach deployed is based on high-throughput experimental screening on representatives which were judiciously selected on the basis of 3-dimensional structural modeling and study of their genetic environments. Applied to DUF849, the method enabled discovery of a large number of activities certain of which were related to a metabolic context. The approach also enabled annotation of the function of the members of the family on the basis of structural motifs.

Moreover, extension of the analysis to other families should enable access to the hidden part of bacterial metabolism.

Crédit : Karine Bastard (UMR Genomics Metabolics)

Diagram of the 3-dimensional structure of the first member of the family whose function was determined.