ESTHER, the database of the α/β-hydrolase fold superfamily of proteins: tools to explore diversity of functions

Abstract

The ESTHER database, which is freely available via a web server (http://bioweb.ensam.inra.fr/esther) and is widely used, is dedicated to proteins with an α/β-hydrolase fold, and it currently contains >30 000 manually curated proteins. Herein, we report those substantial changes towards improvement that we have made to improve ESTHER during the past 8 years since our 2004 update. In particular, we generated 87 new families and increased the coverage of the UniProt Knowledgebase (UniProtKB). We also renewed the ESTHER website and added new visualization tools, such as the Overall Table and the Family Tree. We also address two topics of particular interest to the ESTHER users. First, we explain how the different enzyme classifications (bacterial lipases, peptidases, carboxylesterases) used by different communities of users are combined in ESTHER. Second, we discuss how variations of core architecture or in predicted active site residues result in a more precise clustering of families, and whether this strategy provides trustable hints to identify enzyme-like proteins with no catalytic activity.

Figure 1.

Sequences of putative dienelactone hydrolases where aligned with Clustal Omega (49). The Family Tree was built with FastTree 2 (50), and branches were coloured according to the nature of the nucleophilic residue in the active site. Two families were separated, in blue and red the Dienelactone_hydrolase family and in green the DLH-S family. Blue branches are sequences that have a Cys suitably positioned to be the nucleophilic active site residue, whereas green and red branches have a Ser. Black branches are sequences that have neither Cys nor Ser.