Structural insight into the substrate specificity of PLP fold type IV transaminases

Pyridoxal-5′-phosphate-dependent transaminases of fold type IV (class IV) are promising enzymes for ( R )-selective amination of organic compounds. Transaminases of fold type IV exhibit either strict ( R )-selectivity or ( S )-selectivity that is implemented within geometrically similar active sites of different amino acid compositions. Based on substrate specificity, class IV comprises three large families of transaminases: ( S )-selective branched-chain L-amino acid aminotransferases and ( R )-selective D-amino acid aminotransferases and ( R )-amine:pyruvate transaminases. In this review, we aim to analyze the substrate profiles and correlations between the substrate specificity and organization of the active site in transaminases from these structurally related families. New transaminases with an expanded substrate specificity are also discussed. An analysis of the structural features of substrate binding and comparisons of structural determinants of chiral discrimination between members of the class IV transaminases could be helpful in identifying new biocatalytically relevant enzymes as well as rational protein engineering.