An evolutionary-based approach to design the substrate specificity of the Rossmann fold enzymes

The goal of the project is to infer a detailed evolutionary history of the Rossmann fold, which is one of the most prominent protein folds and by far the most functionally diverse one, with >300 different functions. To this end, we will perform a comprehensive bioinformatics analysis, with the aim of integrating data from different sources to obtain a reliable phylogenetic tree that encompasses all the major Rossmann enzymes classes (NAD(P) dependent dehydrogenases; SAM-dependent methyltransferases; and various NTP-utilizing enzymes).

The ultimate goals of the project are

(i) to reveal the principles that governed the divergence of cofactor specificity of Rossmann enzymes and use these principles to re-engineer cofactor specificity in Rossmann enzymes

(ii) to identify the rudimentary Rossmann fold, and thereby design a functional minimal Rossman.

The project involves experimental validations, including structure determination of re-engineered proteins together with the cofactors.