Dramatic cooperativity in clostridial glutamate dehydrogenase

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The story of GDH was dominated for decades by bovine GDH, commercially available and with complex regualtory behaviour. This story was hampered, however, by the failure to get a crystallographic structure for the enzyme through hte 1970s. 80s and 90s. We deliberately switched around 1980 to a bacterial GDH in the hope of crystals and also in the hope of a cloned gene, DNA sequence and mutagenesis (mammalian genes at that stage being seenas more challenging). This led in collaboration with Davidd Rice's group to the first high-resolution structure for a GDH and accordingly much insight into substrate specificity, catalysis, conezyme specificity etc. Studies of this enzyme also showed that it is allosteric and this is in itself revealing as the bacterial enzyme lacks about 50 amino acids thought to be responsible for allosteric regulation by ADP, GTP etc. in bovine GDH. More recently the structure has finally been solved for bovine GDH showing the 50 residues in question form an antenna region that binds the mononucleotide regulators. The subsequent discussion has seemed to ignore the fact that the hexameric core minus any antenna is already highly allosteric.

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