Abstract
In the transamination reactions undergone by pyridoxal-5'-phosphate-dependent enzymes that act on L-amino acids, the C4' atom of the cofactor is without exception protonated from the si side. This invariant absolute stereochemistry of enzymes not all of which are evolutionarily related to each other and the inverse stereochemistry in the case of D-alanine aminotransferase might reflect a stereochemical constraint in the evolution of these enzymes rather than an accidental historical trait passed on from a common ancestor enzyme. Conceivably, the coenzyme and substrate binding sites of primordial pyridoxal-5'-phosphate-dependent enzymes had to fulfil the following prerequisites in order to allow their development toward effective catalysts: (i) the negatively charged alpha-carboxylate group of the amino acid substrate had to be positioned as far as possible away from the negatively charged phosphate group of the cofactor, and (ii) the C alpha-H bond had to be oriented toward the protein. Compliance with these two criteria implies, under the assumption that C4' is protonated by an acid-base group of the protein, the observed stereochemical feature.
Christen, P