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Title: Regulation of glutamate metabolism by protein kinases in mycobacteria
Authors: O'Hare, Helen M.
Durán, Rosario
Cerveñansky, Carlos
Bellinzoni, Marco
Wehenkel, Anne Marie
Pritsch, Otto
Obal, Gonzalo
Baumgartner, Jens
Vialaret, Jérome
Johnsson, Kai
Alzari, Pedro M.
First Published: 20-Oct-2008
Publisher: Wiley-Blackwell
Citation: Molecular Microbiology, 2008, 70 (6), pp. 1408-1423.
Abstract: Protein kinase G of Mycobacterium tuberculosis has been implicated in virulence and in regulation of glutamate metabolism. Here we show that this kinase undergoes a pattern of autophosphorylation that is distinct from that of other M. tuberculosis protein kinases characterized to date and we identify GarA as a substrate for phosphorylation by PknG. Autophosphorylation of PknG has little effect on kinase activity but promotes binding to GarA, an interaction that is also detected in living mycobacteria. PknG phosphorylates GarA at threonine 21, adjacent to the residue phosphorylated by PknB (T22), and these two phosphorylation events are mutually exclusive. Like the homologue OdhI from Corynebacterium glutamicum, the unphosphorylated form of GarA is shown to inhibit α-ketoglutarate decarboxylase in the TCA cycle. Additionally GarA is found to bind and modulate the activity of a large NAD+-specific glutamate dehydrogenase with an unusually low affinity for glutamate. Previous reports of a defect in glutamate metabolism caused by pknG deletion may thus be explained by the effect of unphosphorylated GarA on these two enzyme activities, which may also contribute to the attenuation of virulence.
ISSN: 0950-382X
Type: Article
Description: This paper was published as Molecular Microbiology, 2008, 70 (6), pp. 1408-1423. The definitive version is available at Doi: 10.1111/j.1365-2958.2008.06489.x
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Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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