Structure of glutamate decarboxylase and related PLP-enzymes: Computer-graphical studies

Amino acid sequences of E. coli glutamate decarboxylase (GADa) and those of 36 GAD of different origin were compared by pairwise alignment using compu ter program CLUSTAL. GAD alpha and plant enzymes showed 59.8-67.8% subunit homology, GADa and other bacterial GAD - 49.8-77.6%, whereas GAD alpha and animal enzymes - 13.9-58.8%. Two PLP-domains exhibited higher homology comp aring to that of the whole subunit in the case of GAD67, plant (68.4-73.995 ), and bacterial (46.7-83.2%) enzymes. The alignment of PLP-domains of 37 G AD, three group II decarboxylases, and two pyridoxal enzymes with known 3D structures (bacterial ORD and mAAT from chicken heart) allowed us to reveal conserved residues of the active sites. Their functional role is discussed . Modelling of the PLP-binding sites in active centers for GAD alpha and hu man brain GAD67 was done using the Swiss-PdbViewer homology modelling progr am. Although the homology between GAD alpha and GAD67 is rather low, struct ural similarity of their active sites allows us to consider here a function al convergence. Thus, glutamate decarboxylation by GAD alpha may be helpful for understanding general mechanism of this reaction.