Structure of Glutamate Decarboxylase and Related PLP-Enzymes: Computer-graphical Studies

Abstract

Amino acid sequences of E. coli glutamate decarboxylase (GADa) and those of 36 GAD of different origin were compared by pairwise alignment using computer program CLUSTAL. GADα and plant enzymes showed 59.8–67.8% subunit homology, GADa and other bacterial GAD—49.8–77.6%, whereas GADα and animal enzymes—13.9–58.8%. Two PLP- domains exhibited higher homology comparing to that of the whole subunit in the case of GAD67, plant (68.4–73.9%), and bacterial (46.7–83.2%) enzymes. The alignment of PLP- domains of 37 GAD, 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 GADα and human brain GAD67 was done using the Swiss- Pdb Viewer homology modelling program. Although the homology between GADα and GAD67 is rather low, structural similarity of their active sites allows us to consider here a functional convergence. Thus, glutamate decarboxylation by GADa may be helpful for understanding general mechanism of this reaction.