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PDBsum entry 1fyc
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Transferase PDB id
1fyc

 

 

 

 

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Contents
Protein chain
106 a.a. *
* Residue conservation analysis
PDB id:
1fyc
Name: Transferase
Title: Inner lipoyl domain from human pyruvate dehydrogenase (pdh) complex, nmr, 1 structure
Structure: Dihydrolipoamide acetyltransferase (e2p). Chain: a. Fragment: lipoyl domain. Engineered: yes. Other_details: dihydrolipoamide acetyltransferase subunit of the pyruvate dehydrogenase (pdh) multienzyme complex (unlipoylated domain)
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: expressed as a gst fusion protein
NMR struc: 1 models
Authors: M.J.Howard,C.Fuller,R.W.Broadhurst,J.Quinn,S.J.Yeaman,R.N.Perham
Key ref: M.J.Howard et al. (1998). Three-dimensional structure of the major autoantigen in primary biliary cirrhosis. Gastroenterology, 115, 139-146. PubMed id: 9649469
Date:
21-Feb-97     Release date:   04-Sep-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10515  (ODP2_HUMAN) -  Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		647 a.a.
106 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.12  - dihydrolipoyllysine-residue acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Oxo-acid dehydrogenase complexes
      Reaction: N6-[(R)-dihydrolipoyl]-L-lysyl-[protein] + acetyl-CoA = N6-[(R)-S(8)- acetyldihydrolipoyl]-L-lysyl-[protein] + CoA
N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein]
 + acetyl-CoA
 = N(6)-[(R)-S(8)- acetyldihydrolipoyl]-L-lysyl-[protein]
 + CoA
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
Gastroenterology 115:139-146 (1998)
PubMed id: 9649469  
 
 
Three-dimensional structure of the major autoantigen in primary biliary cirrhosis.
M.J.Howard, C.Fuller, R.W.Broadhurst, R.N.Perham, J.G.Tang, J.Quinn, A.G.Diamond, S.J.Yeaman.
 
  ABSTRACT  
 
BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. The major autoantigen, recognized by antibodies from > 95% of patients with PBC, has been identified as the E2 component (E2p) of the pyruvate dehydrogenase multienzyme complex. Immunodominant sites on E2p have been localized to the inner of the two lipoyl domains, where the essential cofactor lipoic acid is attached covalently. The aim of this study was to determine the three-dimensional structure of the inner lipoyl domain of human E2p. METHODS: The domain was expressed in Escherichia coli; after purification, its structure was analyzed using nuclear magnetic resonance spectroscopy. RESULTS: The structure of the lipoyl domain from human E2p was determined, and the implications of the structure for autoimmune recognition were assessed. CONCLUSIONS: Knowledge of the structure further defines the major epitope and may help in the design of antigen-specific immunotherapy for treatment of PBC.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20975735 C.Selmi, I.R.Mackay, and M.E.Gershwin (2011).
The autoimmunity of primary biliary cirrhosis and the clonal selection theory.
  Immunol Cell Biol, 89, 70-80.  
20361979 S.Vijayakrishnan, S.M.Kelly, R.J.Gilbert, P.Callow, D.Bhella, T.Forsyth, J.G.Lindsay, and O.Byron (2010).
Solution structure and characterisation of the human pyruvate dehydrogenase complex core assembly.
  J Mol Biol, 399, 71-93.  
19240034 C.A.Brautigam, R.M.Wynn, J.L.Chuang, and D.T.Chuang (2009).
Subunit and catalytic component stoichiometries of an in vitro reconstituted human pyruvate dehydrogenase complex.
  J Biol Chem, 284, 13086-13098.  
18926919 N.Wegner, R.Wait, and P.J.Venables (2009).
Evolutionarily conserved antigens in autoimmune disease: implications for an infective aetiology.
  Int J Biochem Cell Biol, 41, 390-397.  
18609700 J.R.Hov, K.M.Boberg, and T.H.Karlsen (2008).
Autoantibodies in primary sclerosing cholangitis.
  World J Gastroenterol, 14, 3781-3791.  
16263718 E.M.Ciszak, A.Makal, Y.S.Hong, A.K.Vettaikkorumakankauv, L.G.Korotchkina, and M.S.Patel (2006).
How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex.
  J Biol Chem, 281, 648-655.
PDB code: 1zy8
16679318 M.Smolle, A.E.Prior, A.E.Brown, A.Cooper, O.Byron, and J.G.Lindsay (2006).
A new level of architectural complexity in the human pyruvate dehydrogenase complex.
  J Biol Chem, 281, 19772-19780.  
16025495 D.P.Bogdanos, H.Baum, M.Okamoto, P.Montalto, U.C.Sharma, E.I.Rigopoulou, J.Vlachogiannakos, Y.Ma, A.K.Burroughs, and D.Vergani (2005).
Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its Lactobacillus mimic.
  Hepatology, 42, 458-465.  
15861126 M.Kato, J.L.Chuang, S.C.Tso, R.M.Wynn, and D.T.Chuang (2005).
Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex.
  EMBO J, 24, 1763-1774.
PDB codes: 1y8n 1y8o 1y8p
15120760 D.P.Bogdanos, A.Pares, H.Baum, L.Caballeria, E.I.Rigopoulou, Y.Ma, A.K.Burroughs, J.Rodes, and D.Vergani (2004).
Disease-specific cross-reactivity between mimicking peptides of heat shock protein of Mycobacterium gordonae and dominant epitope of E2 subunit of pyruvate dehydrogenase is common in Spanish but not British patients with primary biliary cirrhosis.
  J Autoimmun, 22, 353-362.  
14752820 D.Vergani, D.P.Bogdanos, and H.Baum (2004).
Unusual suspects in primary biliary cirrhosis.
  Hepatology, 39, 38-41.  
12971978 D.E.Jones (2003).
Pathogenesis of primary biliary cirrhosis.
  J Hepatol, 39, 639-648.  
  14724823 S.F.Bruggraber, P.S.Leung, K.Amano, C.Quan, M.J.Kurth, M.H.Nantz, G.D.Benson, J.Van de Water, V.Luketic, T.E.Roche, A.A.Ansari, R.L.Coppel, and M.E.Gershwin (2003).
Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary cirrhosis.
  Gastroenterology, 125, 1705-1713.  
11842080 A.Turkan, X.Gong, T.Peng, and T.E.Roche (2002).
Structural requirements within the lipoyl domain for the Ca2+-dependent binding and activation of pyruvate dehydrogenase phosphatase isoform 1 or its catalytic subunit.
  J Biol Chem, 277, 14976-14985.  
11839747 C.F.Chang, H.T.Chou, J.L.Chuang, D.T.Chuang, and T.H.Huang (2002).
Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex.
  J Biol Chem, 277, 15865-15873.
PDB codes: 1k8m 1k8o
11559360 K.Tozawa, R.W.Broadhurst, A.R.Raine, C.Fuller, A.Alvarez, G.Guillen, G.Padron, and R.N.Perham (2001).
Solution structure of the lipoyl domain of the chimeric dihydrolipoyl dehydrogenase P64K from Neisseria meningitidis.
  Eur J Biochem, 268, 4908-4917.
PDB code: 1gjx
10913250 D.D.Jones, K.M.Stott, M.J.Howard, and R.N.Perham (2000).
Restricted motion of the lipoyl-lysine swinging arm in the pyruvate dehydrogenase complex of Escherichia coli.
  Biochemistry, 39, 8448-8459.
PDB code: 1qjo
11127262 D.E.Jones (2000).
Autoantigens in primary biliary cirrhosis.
  J Clin Pathol, 53, 813-821.  
10966480 R.N.Perham (2000).
Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions.
  Annu Rev Biochem, 69, 961.  
10788482 X.Gong, T.Peng, A.Yakhnin, M.Zolkiewski, J.Quinn, S.J.Yeaman, and T.E.Roche (2000).
Specificity determinants for the pyruvate dehydrogenase component reaction mapped with mutated and prosthetic group modified lipoyl domains.
  J Biol Chem, 275, 13645-13653.  
10441182 I.R.Mackay, J.M.Davies, and M.J.Rowley (1999).
Towards the pathogenesis of autoimmune liver disease.
  J Autoimmun, 13, 163-169.  
10385634 J.M.Palmer, D.E.Jones, J.Quinn, A.McHugh, and S.J.Yeaman (1999).
Characterization of the autoantibody responses to recombinant E3 binding protein (protein X) of pyruvate dehydrogenase in primary biliary cirrhosis.
  Hepatology, 30, 21-26.  
10329614 P.Reche, and R.N.Perham (1999).
Structure and selectivity in post-translational modification: attaching the biotinyl-lysine and lipoyl-lysine swinging arms in multifunctional enzymes.
  EMBO J, 18, 2673-2682.  
  9792103 D.V.Reddy, S.Rothemund, B.C.Shenoy, P.R.Carey, and F.D.Sönnichsen (1998).
Structural characterization of the entire 1.3S subunit of transcarboxylase from Propionibacterium shermanii.
  Protein Sci, 7, 2156-2163.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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