PDBsum entry 2pnr

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protein ligands Protein-protein interface(s) links
Transferase PDB id
Jmol PyMol
Protein chains
374 a.a. *
341 a.a. *
79 a.a. *
RED ×2
Waters ×723
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of the asymmetric pdk3-l2 complex
Structure: [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 3. Chain: a, b, e, f. Synonym: pyruvate dehydrogenase kinase isoform 3. Engineered: yes. Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex. Chain: c, g. Synonym: pyruvate dehydrogenase complex e2 subunit, pdce2,
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pdk3. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: dlat, dlta.
2.50Å     R-factor:   0.176     R-free:   0.229
Authors: D.G.Vassylyev,C.N.Steussy,Y.Devedjiev
Key ref:
Y.Devedjiev et al. (2007). Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications. J Mol Biol, 370, 407-416. PubMed id: 17532006 DOI: 10.1016/j.jmb.2007.04.083
25-Apr-07     Release date:   21-Aug-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q15120  (PDK3_HUMAN) -  [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial
406 a.a.
374 a.a.
Protein chains
Pfam   ArchSchema ?
Q15120  (PDK3_HUMAN) -  [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial
406 a.a.
341 a.a.
Protein chains
Pfam   ArchSchema ?
P10515  (ODP2_HUMAN) -  Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
647 a.a.
79 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: Chains A, B, F, G: E.C.  - [Pyruvate dehydrogenase (acetyl-transferring)] kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
+ [pyruvate dehydrogenase (acetyl-transferring)]
+ [pyruvate dehydrogenase (acetyl-transferring)] phosphate
   Enzyme class 3: Chain C: E.C.  - Dihydrolipoyllysine-residue acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: Acetyl-CoA + enzyme N6-(dihydrolipoyl)lysine = CoA + enzyme N6- (S-acetyldihydrolipoyl)lysine
+ enzyme N(6)-(dihydrolipoyl)lysine
Bound ligand (Het Group name = RED)
matches with 84.00% similarity
= CoA
+ enzyme N(6)- (S-acetyldihydrolipoyl)lysine
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!
  Cellular component     mitochondrion   3 terms 
  Biological process     peroxisome proliferator activated receptor signaling pathway   11 terms 
  Biochemical function     nucleotide binding     8 terms  


DOI no: 10.1016/j.jmb.2007.04.083 J Mol Biol 370:407-416 (2007)
PubMed id: 17532006  
Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications.
Y.Devedjiev, C.N.Steussy, D.G.Vassylyev.
A homodimer of pyruvate dehydrogenase kinase (PDHK) is an integral part of pyruvate dehydrogenase complex (PDC) to which it is anchored primarily through the inner lipoyl-bearing domains (L2) of transacetylase component. The catalytic cycle of PDHK and its translocation over the PDC surface is thought to be mediated by the "symmetric" and "asymmetric" modes, in which the PDHK dimer binds to two and one L2-domain(s), respectively. Whereas the structure of the symmetric PDHK/L2 complex was reported, the structural organization and functional role of the asymmetric complex remain obscure. Here, we report the crystal structure of the asymmetric PDHK3/L2 complex that reveals several functionally important features absent from the previous structures. First, the PDHK3 subunits have distinct conformations: one subunit exhibits "open" and the other "closed" configuration of the putative substrate-binding cleft. Second, access to the closed cleft is additionally restricted by local unwinding of the adjacent alpha-helix. Modeling indicates that the target peptide might gain access to the PDHK active center through the open but not through the closed cleft. Third, the ATP-binding loop in one PDHK3 subunit adopts an open conformation, implying that the nucleotide loading into the active site is mediated by the inactive "pre-insertion" binding mode. Altogether our data suggest that the asymmetric complex represents a physiological state in which binding of a single L2-domain activates one of the PDHK protomers while inactivating another. Thus, the L2-domains likely act not only as the structural anchors but also modulate the catalytic cycle of PDHK.
  Selected figure(s)  
Figure 2.
Figure 2. The gate helices in the L2-free and L2-bound subunits. (a) and (b) The L2-free open (a) and L2-bound (b) configurations of the SC (marked by yellow hydrophobic residues) correspond to the uniform (magenta (a)) and distorted (orange (b)) conformations of the gate helix. The remainder of the subunits is shown in gray. The PDHK active site is marked by the modeled (PDB ID 1Y8P) ATP molecule. (c) and (d) Superposition of the L2-free (magenta (c)) and L2-bound (orange (d)) PDHK gate helices with the RNA polymerase bridge helix (white) observed in the uniform (c) and locally distorted (d) conformations. (e) Stereo view of the L2-bound subunit showing stabilization of the partially unwound gate helix. The hydrogen bonds are shown by magenta broken lines. The active site is marked by ATP as in (a) and (b). The views in (a), (b), and (e) are the same as in Figure 1(b).
Figure 3.
Figure 3. Modeling of the E1/PDHK complex. (a) The overall stereo view of the E1 α-subunit with the modeled α-helical substrate peptide (yellow) docked into the SC of the L2-free PDHK subunit. The E1 β-chain and PDHK L2-bound subunit are located far from the modeled interface and are omitted from the model for clarity. (b) The close-up stereo view of the interface between the E1 substrate α-helix (yellow) and the SC. Hydrophobic side-chains of the substrate are shown in yellow, the phosphorylation site (Ser264) that is modeled in close proximity ( vert, similar 3.3 Å) to the ATP (green) γ-phosphate is colored in orange. The PDHK backbone and hydrophobic side-chains are shown in the domain-dependent colors corresponding to those in (a). The view is roughly the same as in Figure 1(b). (c) Schematic drawing of the putative van der Waals interactions (broken lines) that may be formed between the E1 substrate α-helix and the PDHK hydrophobic residues in the SC. The color scheme is the same as in (a) and (b).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 370, 407-416) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17683942 M.Kato, J.Li, J.L.Chuang, and D.T.Chuang (2007).
Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol.
  Structure, 15, 992.
PDB codes: 2q8f 2q8g 2q8h 2q8i
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