Glutamate dehydrogenase: Structure of a hyperinsulinism mutant, corrections to the atomic model, and insights into a regulatory site.

ABSTRACT: Mammalian glutamate dehydrogenase (GDH) has complex allosteric regulation and the loss of GTP inhibition causes the hyperinsulinism/hyperammonemia syndrome (HHS) where insulin is hypersecreted upon consumption of protein. The archetypical HHS lesion is H454Y and lies in the GTP binding pocket. To better understand the mechanism of HHS, we determined the crystal structure of H454Y. When the bovine GDH crystal structures were minimized to prepare for further computational analysis, unusually large deviations were found at the allosteric NADH binding site due to chemical sequence errors. Notably, 387 lies in an allosteric where several activators and inhibitors bind and should be lysine rather than asparagine. All structures were re-refined and the consequence of this sequence error on NADH b

SUBMITTER: Nassar OM 

PROVIDER: S-EPMC6469361 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature