1W85

The crystal structure of pyruvate dehydrogenase E1 bound to the peripheral subunit binding domain of E2

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 

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This is version 3.1 of the entry. See complete history. 


Literature

A molecular switch and proton wire synchronize the active sites in thiamine enzymes.

Frank, R.A., Titman, C.M., Pratap, J.V., Luisi, B.F., Perham, R.N.

(2004) Science 306: 872-876

  • DOI: https://doi.org/10.1126/science.1101030
  • Primary Citation of Related Structures:  
    1W85, 1W88

  • PubMed Abstract: 

    Thiamine diphosphate (ThDP) is used as a cofactor in many key metabolic enzymes. We present evidence that the ThDPs in the two active sites of the E1 (EC 1.2.4.1) component of the pyruvate dehydrogenase complex communicate over a distance of 20 angstroms by reversibly shuttling a proton through an acidic tunnel in the protein. This "proton wire" permits the co-factors to serve reciprocally as general acid/base in catalysis and to switch the conformation of crucial active-site peptide loops. This synchronizes the progression of chemical events and can account for the oligomeric organization, conformational asymmetry, and "ping-pong" kinetic properties of E1 and other thiamine-dependent enzymes.

    • Organizational Affiliation: 

    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PYRUVATE DEHYDROGENASE E1 COMPONENT, ALPHA SUBUNIT
A, C, E, G
368Geobacillus stearothermophilusMutation(s): 0 
EC: 1.2.4.1
UniProt
Find proteins for P21873 (Geobacillus stearothermophilus)
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Go to UniProtKB:  P21873
Entity Groups  
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UniProt GroupP21873
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PYRUVATE DEHYDROGENASE E1 COMPONENT, BETA SUBUNIT
B, D, F, H
324Geobacillus stearothermophilusMutation(s): 0 
EC: 1.2.4.1
UniProt
Find proteins for P21874 (Geobacillus stearothermophilus)
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Go to UniProtKB:  P21874
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UniProt GroupP21874
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
DIHYDROLIPOYLLYSINE-RESIDUE ACETYLTRANSFERASE COMPONENT OF PYRUVATE
I, J
49Geobacillus stearothermophilusMutation(s): 0 
EC: 2.3.1.12
UniProt
Find proteins for P11961 (Geobacillus stearothermophilus)
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Go to UniProtKB:  P11961
Entity Groups  
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UniProt GroupP11961
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TPP
Query on TPP
Download Ideal Coordinates CCD File 
M [auth A],
R [auth C],
U [auth E],
Z [auth G]		THIAMINE DIPHOSPHATE
C12 H19 N4 O7 P2 S
AYEKOFBPNLCAJY-UHFFFAOYSA-O
PEG
Query on PEG
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L [auth A],
Q [auth C],
Y [auth G]		DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
K
Query on K
Download Ideal Coordinates CCD File 
AA [auth H],
N [auth B],
S [auth D],
V [auth F]		POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
MG
Query on MG
Download Ideal Coordinates CCD File 
K [auth A]
O [auth B]
P [auth C]
T [auth E]
W [auth F]
K [auth A],
O [auth B],
P [auth C],
T [auth E],
W [auth F],
X [auth G]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.27α = 90
b = 232.33β = 90.81
c = 91.924γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-11-02
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2019-05-08
    Changes: Atomic model, Data collection, Database references, Experimental preparation, Other
  • Version 3.0: 2021-08-04
    Changes: Atomic model, Data collection, Derived calculations, Non-polymer description, Other, Structure summary
  • Version 3.1: 2023-12-13
    Changes: Data collection, Database references, Refinement description