Document Detail


A dual conformation of the post-decarboxylation intermediate is associated with distinct enzyme states in mycobacterial KGD (α-ketoglutarate decarboxylase).
MedLine Citation:
PMID:  24171907     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Tristan Wagner; Nathalie Barilone; Pedro M Alzari; Marco Bellinzoni
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  457     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-01-13     Completed Date:  2014-03-18     Revised Date:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  425-34     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
PDB/3ZHQ;  3ZHR;  3ZHS;  3ZHT;  3ZHU;  3ZHV
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MeSH Terms
Descriptor/Qualifier:
Adipates / chemistry,  metabolism
Aldehyde-Ketone Transferases / chemistry,  genetics,  metabolism
Amino Acid Substitution
Bacterial Proteins / chemistry,  genetics,  metabolism*
Biocatalysis
Carboxy-Lyases / chemistry,  genetics,  metabolism*
Catalytic Domain
Decarboxylation
Ketoglutarate Dehydrogenase Complex / chemistry,  genetics,  metabolism
Ketoglutaric Acids / chemistry,  metabolism
Models, Molecular*
Molecular Conformation
Molecular Docking Simulation
Mutant Proteins / chemistry,  metabolism
Mycobacterium smegmatis / enzymology*
Peptide Fragments / chemistry,  genetics,  metabolism
Protein Processing, Post-Translational*
Protein Refolding*
Recombinant Proteins / chemistry,  metabolism
Chemical
Reg. No./Substance:
0/Adipates; 0/Bacterial Proteins; 0/Ketoglutaric Acids; 0/Mutant Proteins; 0/Peptide Fragments; 0/Recombinant Proteins; 328-50-7/alpha-ketoglutaric acid; BB72FKL1M2/alpha-ketoadipic acid; EC 1.2.4.2/Ketoglutarate Dehydrogenase Complex; EC 2.2.-/Aldehyde-Ketone Transferases; EC 2.2.1.5/2-hydroxy-3-oxoadipate synthase; EC 4.1.1.-/Carboxy-Lyases; EC 4.1.1.71/2-oxoglutarate decarboxylase
Comments/Corrections
Erratum In:
Biochem J. 2014 Mar 1;458(2):419

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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