Structure and stereochemistry of the substrate-coenzyme bond in ternary complexes

Structure and stereochemistry of the substrate-coenzyme bond in ternary complexes 

The above approach has also been extended to the study of the solvent sidedness of the face of the substrate-coenzyme Schiff base, in a ternary complex. During the normal functioning of a pyridoxal-P-dependent enzyme several types of ternary complex will be present, although only two species represented by structures 1 and 2 

Similar experimental approaches have been extended to the reduction of substrate-coenzyme Schiff bases in two other ternary complexes. In the case of tyrosine decarboxylase [103], the ternary complex produced from the physiological substrate, L-tyrosine, was used in the trapping, while with tryptophanase [104], a reducable ternary complex was generated using L-alanine, a competitive inhibitor for the enzyme. In these two cases, once again it was the Si face at C-4 of the substrate-coenzyme Schiff base in the ternary complex that was available for attack by NaBH4. These results provide an interesting contrast with the Re face attack 

The pattern recorded above raises the question whether the change of face at C-4 to the solvent side is a mandatory requirement in the transformation of binary into ternary complexes in pyridoxal-P-dependent reactions. That this may be so was the view beginning to prevail until a timely reminder, or perhaps an undue caution, came from a more recent report by Zito and Martinez-Carrion [93]. As has already been cited, these workers repeated the earlier experiments of the Zurich School on aspartate aminotransferase confirming the Re face hydride attack at C-4 in the binary complex. However, aspartate aminotransferase carbamylated at the active site Lys-258 was used to produce the substrate-coenzyme Schiff base linkage in the ternary complex. Since the modified enzyme catalysed the half-transamination reaction  

Notwithstanding this, several explanations have been, or can be, offered to rationalise the opposite stereochemical modes of the reduction of the Schiff bases in the binary and ternary complexes and these are considered below. 

---