کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2200951 1099988 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A marriage full of surprises; forty-five years living with glutamate dehydrogenase
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
A marriage full of surprises; forty-five years living with glutamate dehydrogenase
چکیده انگلیسی

Detailed kinetic studies of bovine glutamate dehydrogenase [GDH] from the 1960s revealed complexities that remain to be fully explained. In the absence of heterotropic nucleotide regulators the enzyme follows a random pathway of substrate addition but saturation with ADP enforces a compulsory-order mechanism in which glutamate is the leading substrate. The rate dependence on NAD(P)+ concentration is complex and is probably only partly explained by negative binding cooperativity. Bovine GDH eluded successful analysis by crystallographers for 30 years but the final structural solution presented in this symposium at last provides a comprehensible framework for much of the heterotropic regulation, focussing attention on an antenna region in the C-terminal tail, a structure that is missing in the slightly smaller hexameric GDHs of lower organisms. Nonetheless, our studies with one such smaller (clostridial) GDH reveal that even without the antenna the underlying core structure still mediates homotropic cooperativity, and the ability to generate a variety of mutants has made it possible to start to dissect this machinery.In addition, this short personal review discusses a number of unresolved issues such as the significance of phospholipid inhibition and of specific interaction with mRNA, and above all the question of why it is necessary to regulate an enzyme reputedly maintaining its reactants at equilibrium and whether this might be in some way related to its coexistence with an energy-linked transhydrogenase.


► Random substrate addition but with saturating ADP glutamate leads.
► Kinetic/regulatory properties are profoundly influenced by buffer choice.
► Complexity of homotropic regulation by NAD(P)+ is not yet fully explained.
► Core hexameric GDHs lacking the C-terminal antenna are still allosteric.
► Site-directed mutagenesis probes basis of inter-site communication.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 59, Issue 4, September 2011, Pages 489–494
نویسندگان
,