DescriptionPyridoxal-5’-phosphate (PLP)-dependent enzymes are mainly involved in the amino acids metabolism and catalyze a number of diverse chemicals reactions, such as decarboxylation, transamination, racemization, elimination, carbon-carbon bond cleavage and formation. Due to remarkable versatility of the PLP-enzymes they have been exploited as biocatalysts for the production of natural and non-natural amino acids and their related compounds. All structurally characterized PLP-dependent enzymes have been classified into five distinct structural families. Enzymes belonging to one family often exhibit diverse functions and/or broad substrate ranges. To explore the molecular basis of the functional diversity in the aspartate aminotransferase family of PLP-dependent enzymes, e.g. substrate and reaction specificity, the comparative bioinformatic analysis of genetic and structural data of homologous proteins was carried out. The approach applies a multiple structural based sequence alignment of evolutionary related proteins, which was further used to cluster the proteins into subfamilies according to their functional diversity. Systematic analysis of the amino acids distribution within subfamilies combined with detailed investigation of the structural differences between functionally different enzymes enabled identification of the subfamily-specific positions and structural elements (e.g. cofactor and substrate binding regions) responsible for the catalytic diversity in each subfamily. Thus selected specific positions were used as hotspots for rational engineering of L-threonine aldolase to reveal the putative amino acid positions that mediate catalytic activity and substrate specificity in this class of enzymes. This knowledge will be prerequisite to design the efficient biocatalysts for the asymmetric synthesis of non-canonical amino acids.
|Period||10 Jul 2016 → 15 Jul 2016|
|Event title||Gordon Research Conference on Biocatalysis|
|Location||Biddeford, United States, Maine|
|Degree of Recognition||International|