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Functional plasticity and allosteric regulation of α-ketoglutarate decarboxylase in central mycobacterial metabolism.

Wagner T, Bellinzoni M, Wehenkel A, O'Hare HM, Alzari PM
Chem Biol 18 1011-20 (2011)
Related entries: 2xt6, 2xta, 2y0p, 2yid

Cited: 45 times
EuropePMC logo PMID: 21867916

Abstract

The α-ketoglutarate dehydrogenase (KDH) complex is a major regulatory point of aerobic energy metabolism. Mycobacterium tuberculosis was reported to lack KDH activity, and the putative KDH E1o component, α-ketoglutarate decarboxylase (KGD), was instead assigned as a decarboxylase or carboligase. Here, we show that this protein does in fact sustain KDH activity, as well as the additional two reactions, and these multifunctional properties are shared by the Escherichia coli homolog, SucA. We also show that the mycobacterial enzyme is finely regulated by an additional acyltransferase-like domain and by the action of acetyl-CoA, a powerful allosteric activator able to enhance the concerted protein motions observed during catalysis. Our results uncover the functional plasticity of a crucial node in bacterial metabolism, which may be important for M. tuberculosis during host infection.

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