3ZHV

Crystal structure of the SucA domain of Mycobacterium smegmatis KGD, post-decarboxylation intermediate from pyruvate (2-hydroxyethyl-ThDP)

Summary for 3ZHV

• Entry DOI: 10.2210/pdb3zhv/pdb
• Related: 3ZHQ 3ZHR 3ZHS 3ZHT 3ZHU
• Descriptor: MULTIFUNCTIONAL 2-OXOGLUTARATE METABOLISM ENZYME, 2-[3-[(4-azanyl-2-methyl-pyrimidin-5-yl)methyl]-4-methyl-2-[(1S)-1-oxidanylethyl]-1,3-thiazol-3-ium-5-yl]ethyl phosphono hydrogen phosphate, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase, e1o
• Biological source: MYCOBACTERIUM SMEGMATIS
• Total number of polymer chains: 4
• Total formula weight: 390801.59

Authors

Wagner, T.,Barilone, N.,Bellinzoni, M.,Alzari, P.M. (deposition date: 2012-12-24, release date: 2013-11-13, Last modification date: 2023-12-20)

Primary citation

Wagner, T.,Barilone, N.,Alzari, P.M.,Bellinzoni, M.
A Dual Conformation of the Post-Decarboxylation Intermediate is Associated with Distinct Enzyme States in Mycobacterial Alpha-Ketoglutarate Decarboxylase (Kgd).
Biochem.J., 457:425-, 2014

PubMed Abstract: α-Ketoacid dehydrogenases are large multi-enzyme machineries that orchestrate the oxidative decarboxylation of α-ketoacids with the concomitant production of acyl-CoA and NADH. The first reaction, catalysed by α-ketoacid decarboxylases (E1 enzymes), needs a thiamine diphosphate cofactor and represents the overall rate-limiting step. Although the catalytic cycles of E1 from the pyruvate dehydrogenase (E1p) and branched-chain α-ketoacid dehydrogenase (E1b) complexes have been elucidated, little structural information is available on E1o, the first component of the α-ketoglutarate dehydrogenase complex, despite the central role of this complex at the branching point between the TCA (tricarboxylic acid) cycle and glutamate metabolism. In the present study, we provide structural evidence that MsKGD, the E1o (α-ketoglutarate decarboxylase) from Mycobacterium smegmatis, shows two conformations of the post-decarboxylation intermediate, each one associated with a distinct enzyme state. We also provide an overall picture of the catalytic cycle, reconstructed by either crystallographic snapshots or modelling. The results of the present study show that the conformational change leading the enzyme from the initial (early) to the late state, although not required for decarboxylation, plays an essential role in catalysis and possibly in the regulation of mycobacterial E1o.

PubMed: 24171907
DOI: 10.1042/BJ20131142

Experimental method

X-RAY DIFFRACTION (2.3 Å)