X-ray Crystallographic Study on AspAT

High resolution crystallographic studies have demonstrated that AspAT has open and closed conformations. Upon the binding of a substrate which favors the closed conformation, the small domain rotates so that the active site residues are brought closer to the substrate moiety. This movement of the small domain is important for initiation of the catalytic reaction. Therefore, the closed conformation is believed to represent the functional states of the enzyme.291 Three distinct crystal forms of mAspAT were analyzed, namely triclinic crystal for open conformation, monoclinic and orthorhombic crystals for closed conformation. The enzymes cocrystallized with substrate analogs seemed to have a tendency to assume the closed conformation.28 291 The order of this tendency was shown to be apoenzyme1 PLP form of the enzyme PMP form of the enzyme. 

Although highly refined X-ray structures of AspAT are available, they do not provide an explanation for the subtle differences that occur when AspAT binds to various substrates. Such subtle differences have been distinguished by the kinetic analysis, however. 

It is of interest to compare the tertiary structure of AspAT with that of other PLP-dependent enzymes. Some PLP enzymes whose primary structures are quite different from AspAT exhibit similar tertiary structures. Such enzymes are a -amino acid pyruvate aminotransferase,341 phosphoserine aminotransferase351 and tyrosine-phenol lyase361 (Phillips, R., personal communication). Similarity in tertiary structure among these PLP enzymes may lead to the idea that many PLP-dependent enzymes share the same ancestor protein. There are PLP enzymes belonging to its own category, such as glycogen phosphorylase and tryptophan synthase.37 381 These enzymes do not share any similarities in either primary or tertiary structures with AspAT. 

---