PDBsum entry 3b8k

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protein links
Transferase PDB id
Protein chain
239 a.a. *
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of the truncated human dihydrolipoyl acetyltransferase (e2)
Structure: Dihydrolipoyllysine-residue acetyltransferase. Chain: a. Fragment: c-terminal catalytic domain. Synonym: pyruvate dehydrogenase complex e2 subunit. Pdce2. E2. Dihydrolipoamide s- acetyltransferase component of pyruvate dehydrogenase complex. Pdc-e2. 70 kda mitochondrial autoantigen of primary biliary cirrhosis. Pbc. M2 antigen complex 70 kda subunit. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: dlat, dlta. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Authors: X.Yu,Y.Hiromasa,H.Tsen,J.K.Stoops,T.E.Roche,Z.H.Zhou
Key ref:
X.Yu et al. (2008). Structures of the human pyruvate dehydrogenase complex cores: a highly conserved catalytic center with flexible N-terminal domains. Structure, 16, 104-114. PubMed id: 18184588 DOI: 10.1016/j.str.2007.10.024
01-Nov-07     Release date:   22-Jan-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P10515  (ODP2_HUMAN) -  Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
647 a.a.
239 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     transferase activity, transferring acyl groups     1 term  


DOI no: 10.1016/j.str.2007.10.024 Structure 16:104-114 (2008)
PubMed id: 18184588  
Structures of the human pyruvate dehydrogenase complex cores: a highly conserved catalytic center with flexible N-terminal domains.
X.Yu, Y.Hiromasa, H.Tsen, J.K.Stoops, T.E.Roche, Z.H.Zhou.
Dihydrolipoyl acetyltransferase (E2) is the central component of pyruvate dehydrogenase complex (PDC), which converts pyruvate to acetyl-CoA. Structural comparison by cryo-electron microscopy (cryo-EM) of the human full-length and truncated E2 (tE2) cores revealed flexible linkers emanating from the edges of trimers of the internal catalytic domains. Using the secondary structure constraints revealed in our 8 A cryo-EM reconstruction and the prokaryotic tE2 atomic structure as a template, we derived a pseudo atomic model of human tE2. The active sites are conserved between prokaryotic tE2 and human tE2. However, marked structural differences are apparent in the hairpin domain and in the N-terminal helix connected to the flexible linker. These permutations away from the catalytic center likely impart structures needed to integrate a second component into the inner core and provide a sturdy base for the linker that holds the pyruvate dehydrogenase for access by the E2-bound regulatory kinase/phosphatase components in humans.
  Selected figure(s)  
Figure 5.
Figure 5. Cryo-EM Density-Restrained Atomic Modeling of Human tE2
(A) Wire-frame representation of a high-resolution cryo-EM density map from Figure 3, superimposed with our cryo-EM-derived pseudo atomic model (gold ribbon) (also see Movie S1).
(B and C) Close-up views of two neighboring tE2 monomers (in different colors), shown either (B) with or (C) without the cryo-EM density superimposed. Arrows in (C) indicate the C-terminal helix H7 that is involved in the interaction between two E2 monomers.
(D and E) Close-up views of two representative regions of a single E2 trimer, showing agreement of the disposition of secondary structure elements between the cryo-EM densities (wire-frame) and the pseudo atomic model (ribbon). Different colors represent structure elements from different tE2 monomers.
(F) Close-up view of the internal hairpin loop region of tE2, showing the cryo-EM density (wire-frame), the unrefined homology model (blue ribbon), and the refined, cryo-EM-restrained model (gold ribbon).
Figure 6.
Figure 6. Comparison of Human and Prokaryotic tE2 Structures and Mechanistic Model of Human PDC Function
(A–C) The human (purple and red) and A. vinelandii (gold) (Mattevi et al., 1992) tE2 structures are superimposed and are shown in three approximately orthogonal views. The helices (H) and β strands (S) are numbered consecutively from the N to C termini. (A) The highly conserved β barrel region of the tE2 trimers. For clarity, only the internal β barrel center region of the trimer is shown, and this region consists of β strands and a flanking helix from each of the three tE2 subunits. One subunit of human tE2 is colored red. (B and C) Orthogonal views of the superposition of the human (purple) and A. vinelandii (gold) tE2 monomer showing the most significant structural differences located in the N-terminal loop and its connected helix (H1), and the internal hairpin loop. In (C), coenzyme A (CoA) is shown as a ball-and-stick model to highlight the location of the conserved active sites in the two models (Mattevi et al., 1992).
(D) Proposed model of human PDC structural organization and mechanism for catalysis and regulation (see details in Movie S3). Six E3BP dimmers (brown) substitute for 12 E2 subunits (purple) to form the E2•E3BP core as described (Hiromasa et al., 2004). Around each pentagonal opening, one E3 and two E1 molecules interact to form a shell connected to the E2•E3BP core through 50 Å linkers. The catalytic intermediates and regulatory enzymes are transferred through the “swinging arm” and “hand-over-hand” walking mechanisms. Abbreviations: E1BD, E1-binding domain; E3BD, E3-binding domain; LpD, lipoyl domain.
  The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 104-114) copyright 2008.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20180236 S.Braun, C.Berg, S.Buck, M.Gregor, and R.Klein (2010).
Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis.
  World J Gastroenterol, 16, 973-981.  
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.  
18514542 D.H.Chen, J.Jakana, X.Liu, M.F.Schmid, and W.Chiu (2008).
Achievable resolution from images of biological specimens acquired from a 4k x 4k CCD camera in a 300-kV electron cryomicroscope.
  J Struct Biol, 163, 45-52.  
18658136 R.M.Wynn, M.Kato, J.L.Chuang, S.C.Tso, J.Li, and D.T.Chuang (2008).
Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity.
  J Biol Chem, 283, 25305-25315.
PDB codes: 2zkj 3d2r
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