Structural features and regulatory properties of the brain glutamate decarboxylases.

摘要: Abstract It is widely recognized that the two major forms of GAD present in adult vertebrate brains are each composed sequence domains differ size and degree similarity. The amino-terminal domain smaller shows little identity between forms. This thought to mediate subcellular targeting GADs. Substantial parts appear be exposed flexible, as shown by proteolysis experiments locations posttranslational modifications. carboxyl-terminal contains catalytic site substantial similarity interaction with its cofactor, pyridoxal-5′ phosphate (pyridoxal-P), plays a key role regulation activity. Although GAD65 GAD67 interact differently pyridoxal-P, their cofactor-binding sites contain same set nine putative residues have basic structural fold. Thus differences cannot attributed fundamental GADs but must result from subtle modifications presence another conserved motif suggests functional domains: small closes when substrate binds. Finally, dimeric enzyme features superfamily pyridoxal-P proteins indicate dimer-forming interactions mediated mainly domain.