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Oxidoreductase PDB id
2bp7
Jmol
Contents
Protein chains
407 a.a. *
338 a.a. *
Waters ×138
* Residue conservation analysis
PDB id:
2bp7
Name: Oxidoreductase
Title: New crystal form of the pseudomonas putida branched-chain dehydrogenase (e1)
Structure: 2-oxoisovalerate dehydrogenase alpha subunit. Chain: a, c, e, g. Synonym: branched-chain dehydrogenase e1, branched-chain alpha-keto acid dehydrogenase e1 component alpha chain, bckdh e1-alpha. Engineered: yes. 2-oxoisovalerate dehydrogenase beta subunit. Chain: b, d, f, h. Synonym: branched-chain dehydrogenase e1, branched-chain
Source: Pseudomonas putida. Organism_taxid: 303. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.9Å     R-factor:   0.228     R-free:   0.254
Authors: R.A.W.Frank,J.V.Pratap,X.Y.Pei,R.N.Perham,B.F.Luisi
Key ref:
R.A.Frank et al. (2005). The molecular origins of specificity in the assembly of a multienzyme complex. Structure (Camb), 13, 1119-1130. PubMed id: 16084384 DOI: 10.1016/j.str.2005.04.021
Date:
18-Apr-05     Release date:   10-Aug-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P09060  (ODBA_PSEPU) -  2-oxoisovalerate dehydrogenase subunit alpha
Seq:
Struc: 		410 a.a.
407 a.a.
Protein chains
Pfam   ArchSchema ?
P09061  (ODBB_PSEPU) -  2-oxoisovalerate dehydrogenase subunit beta
Seq:
Struc: 		339 a.a.
338 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.1.2.4.4  - 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Oxo-acid dehydrogenase complexes
      Reaction: 3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine- residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO2
3-methyl-2-oxobutanoate
 + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine
 = [dihydrolipoyllysine- residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine
 + CO(2)
      Cofactor: Thiamine diphosphate
Thiamine diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.str.2005.04.021 Structure (Camb) 13:1119-1130 (2005)
PubMed id: 16084384  
 
 
The molecular origins of specificity in the assembly of a multienzyme complex.
R.A.Frank, J.V.Pratap, X.Y.Pei, R.N.Perham, B.F.Luisi.
 
  ABSTRACT  
 
The pyruvate dehydrogenase (PDH) multienzyme complex is central to oxidative metabolism. We present the first crystal structure of a complex between pyruvate decarboxylase (E1) and the peripheral subunit binding domain (PSBD) of the dihydrolipoyl acetyltransferase (E2). The interface is dominated by a "charge zipper" of networked salt bridges. Remarkably, the PSBD uses essentially the same zipper to alternately recognize the dihydrolipoyl dehydrogenase (E3) component of the PDH assembly. The PSBD achieves this dual recognition largely through the addition of a network of interfacial water molecules unique to the E1-PSBD complex. These structural comparisons illuminate our observations that the formation of this water-rich E1-E2 interface is largely enthalpy driven, whereas that of the E3-PSBD complex (from which water is excluded) is entropy driven. Interfacial water molecules thus diversify surface complementarity and contribute to avidity, enthalpically. Additionally, the E1-PSBD structure provides insight into the organization and active site coupling within the approximately 9 MDa PDH complex.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Catalytic Mechanism of PDH and the Structure of E1-PSBD
(A) Catalytic mechanism of the pyruvate dehydrogenase multienzyme complex. Reactions catalyzed by E1, E2, and E3 are shown by red, green, and yellow arrows, respectively.
(B) E1-PSBD structure. A ribbon diagram of the complete E1 heterotetramer bound to the PSBD of E2. Two views are shown related by a 90° rotation. A color key for the domains of each subunit is shown. E1 a* and b* are the subunits that form an active site in the "closed" state, whereas the a and b chains making the second active site are in the "open state." The PSBD from E2, colored green, binds on the 2-fold interface of two C-terminal domains of the E1 b chains (colored cyan and orange). Thiamine diphosphate and Mg2+ ions are highlighted as space-filled atoms. The entrances to the active sites in "closed" and "open" states are shown by black (to the foreground) and gray (to the background) arrows, respectively. Figures were made with PyMOL (DeLano, 2003).
 
  The above figure is reprinted by permission from Cell Press: Structure (Camb) (2005, 13, 1119-1130) copyright 2005.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20662005 E.Arbely, H.Neuweiler, T.D.Sharpe, C.M.Johnson, and A.R.Fersht (2010).
The human peripheral subunit-binding domain folds rapidly while overcoming repulsive Coulomb forces.
  Protein Sci, 19, 1704-1713.  
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.  
19594830 M.G.Posner, A.Upadhyay, S.Bagby, D.W.Hough, and M.J.Danson (2009).
A unique lipoylation system in the Archaea. Lipoylation in Thermoplasma acidophilum requires two proteins.
  FEBS J, 276, 4012-4022.  
20160912 M.S.Patel, L.G.Korotchkina, and S.Sidhu (2009).
Interaction of E1 and E3 components with the core proteins of the human pyruvate dehydrogenase complex.
  J Mol Catal B Enzym, 61, 2-6.  
19675886 M.Sunbul, and J.Yin (2009).
Site specific protein labeling by enzymatic posttranslational modification.
  Org Biomol Chem, 7, 3361-3371.  
18184587 J.S.Lengyel, K.M.Stott, X.Wu, B.R.Brooks, A.Balbo, P.Schuck, R.N.Perham, S.Subramaniam, and J.L.Milne (2008).
Extended polypeptide linkers establish the spatial architecture of a pyruvate dehydrogenase multienzyme complex.
  Structure, 16, 93.  
18206651 L.G.Korotchkina, and M.S.Patel (2008).
Binding of pyruvate dehydrogenase to the core of the human pyruvate dehydrogenase complex.
  FEBS Lett, 582, 468-472.  
19081061 M.Kato, R.M.Wynn, J.L.Chuang, S.C.Tso, M.Machius, J.Li, and D.T.Chuang (2008).
Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops.
  Structure, 16, 1849-1859.
PDB codes: 3exe 3exf 3exg 3exh 3exi
18316329 T.Nakai, S.Kuramitsu, and N.Kamiya (2008).
Structural bases for the specific interactions between the E2 and E3 components of the Thermus thermophilus 2-oxo acid dehydrogenase complexes.
  J Biochem, 143, 747-758.  
18004749 V.I.Bunik, and D.Degtyarev (2008).
Structure-function relationships in the 2-oxo acid dehydrogenase family: substrate-specific signatures and functional predictions for the 2-oxoglutarate dehydrogenase-like proteins.
  Proteins, 71, 874-890.  
19081062 X.Y.Pei, C.M.Titman, R.A.Frank, F.J.Leeper, and B.F.Luisi (2008).
Snapshots of catalysis in the E1 subunit of the pyruvate dehydrogenase multienzyme complex.
  Structure, 16, 1860-1872.
PDB codes: 3duf 3dv0 3dva
16442803 C.A.Brautigam, R.M.Wynn, J.L.Chuang, M.Machius, D.R.Tomchick, and D.T.Chuang (2006).
Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex.
  Structure, 14, 611-621.
PDB codes: 2f5z 2f60
16861235 C.F.Chang, H.T.Chou, Y.J.Lin, S.J.Lee, J.L.Chuang, D.T.Chuang, and T.H.Huang (2006).
Structure of the subunit binding domain and dynamics of the di-domain region from the core of human branched chain alpha-ketoacid dehydrogenase complex.
  J Biol Chem, 281, 28345-28353.  
16308322 J.L.Milne, X.Wu, M.J.Borgnia, J.S.Lengyel, B.R.Brooks, D.Shi, R.N.Perham, and S.Subramaniam (2006).
Molecular structure of a 9-MDa icosahedral pyruvate dehydrogenase subcomplex containing the E2 and E3 enzymes using cryoelectron microscopy.
  J Biol Chem, 281, 4364-4370.  
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.  
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 codes are shown on the right.