2XT6

Crystal structure of Mycobacterium smegmatis alpha-ketoglutarate decarboxylase homodimer (orthorhombic form)

Summary for 2XT6

• Entry DOI: 10.2210/pdb2xt6/pdb
• Related: 2XT5 2XT7 2XT8 2XT9 2XTA
• Descriptor: 2-OXOGLUTARATE DECARBOXYLASE, THIAMINE DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: lyase, kdh, kgd
• Biological source: MYCOBACTERIUM SMEGMATIS
• Total number of polymer chains: 2
• Total formula weight: 249172.00

Authors

Wagner, T.,Bellinzoni, M.,Wehenkel, A.M.,O'Hare, H.M.,Alzari, P.M. (deposition date: 2010-10-05, release date: 2011-06-15, Last modification date: 2023-12-20)

Primary citation

Wagner, T.,Bellinzoni, M.,Wehenkel, A.M.,O'Hare, H.M.,Alzari, P.M.
Functional Plasticity and Allosteric Regulation of Alpha-Ketoglutarate Decarboxylase in Central Mycobacterial Metabolism.
Chem.Biol., 18:1011-, 2011

PubMed 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.

PubMed: 21867916
DOI: 10.1016/J.CHEMBIOL.2011.06.004

Experimental method

X-RAY DIFFRACTION (2.74 Å)