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PDBsum entry 3zhv

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
3zhv
Jmol
Contents
Protein chains
820 a.a.
Ligands
TDW ×4
Metals
_CA ×4
_MG ×4
Waters ×969
PDB id:
3zhv
Name: Oxidoreductase
Title: Crystal structure of the suca domain of mycobacterium smegma post-decarboxylation intermediate from pyruvate (2-hydroxyethyl-thdp)
Structure: Multifunctional 2-oxoglutarate metabolism enzyme. Chain: a, b, c, d. Fragment: suca-like catalytic domain, residues 361-1227. Synonym: 2-hydroxy-3-oxoadipate synthase, hoa synthase, hoa 2-oxoglutarate carboxy-lyase, 2-oxoglutarate decarboxylase alpha-ketoglutarate decarboxylase, kg decarboxylase, kgd, alpha-ketoglutarate-glyoxylate carboligase, 2-oxoglutarate dehydrogenase e1 component, odh e1 component, alpha-ketogl dehydrogenase e1 component, kdh e1 component,
Source: Mycobacterium smegmatis. Organism_taxid: 1772. Strain: mc2_155. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plyss.
Resolution:
2.30Å     R-factor:   0.205     R-free:   0.235
Authors: T.Wagner,N.Barilone,M.Bellinzoni,P.M.Alzari
Key ref: T.Wagner et al. (2014). A dual conformation of the post-decarboxylation intermediate is associated with distinct enzyme states in mycobacterial KGD (α-ketoglutarate decarboxylase). Biochem J, 457, 425-434. PubMed id: 24171907 DOI: 10.1042/BJ20131142
Date:
24-Dec-12     Release date:   13-Nov-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
A0R2B1  (KGD_MYCS2) -  Multifunctional 2-oxoglutarate metabolism enzyme
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1227 a.a.
820 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.1.2.4.2  - Oxoglutarate dehydrogenase (succinyl-transferring).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Oxo-acid dehydrogenase complexes
      Reaction: 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2
2-oxoglutarate
+ [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine
= [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine
+ CO(2)
      Cofactor: Thiamine diphosphate
Thiamine diphosphate
Bound ligand (Het Group name = TDW) matches with 89.66% similarity
   Enzyme class 3: E.C.2.2.1.5  - 2-hydroxy-3-oxoadipate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: 2-oxoglutarate + glyoxylate = 2-hydroxy-3-oxoadipate + CO2
2-oxoglutarate
+ glyoxylate
= 2-hydroxy-3-oxoadipate
+ CO(2)
      Cofactor: Thiamine diphosphate
Thiamine diphosphate
Bound ligand (Het Group name = TDW) matches with 89.66% similarity
   Enzyme class 4: E.C.2.3.1.61  - Dihydrolipoyllysine-residue succinyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: Succinyl-CoA + enzyme N6-(dihydrolipoyl)lysine = CoA + enzyme N6- (S-succinyldihydrolipoyl)lysine
Succinyl-CoA
+ enzyme N(6)-(dihydrolipoyl)lysine
= CoA
+ enzyme N(6)- (S-succinyldihydrolipoyl)lysine
   Enzyme class 5: E.C.4.1.1.71  - 2-oxoglutarate decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2-oxoglutarate = succinate semialdehyde + CO2
2-oxoglutarate
= succinate semialdehyde
+ CO(2)
      Cofactor: Thiamine diphosphate
Thiamine diphosphate
Bound ligand (Het Group name = TDW) matches with 89.66% similarity
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   3 terms 
  Biochemical function     thiamine pyrophosphate binding     3 terms  

 

 
    reference    
 
 
DOI no: 10.1042/BJ20131142 Biochem J 457:425-434 (2014)
PubMed id: 24171907  
 
 
A dual conformation of the post-decarboxylation intermediate is associated with distinct enzyme states in mycobacterial KGD (α-ketoglutarate decarboxylase).
T.Wagner, N.Barilone, P.M.Alzari, M.Bellinzoni.
 
  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.