1W85

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

PDB DOI: https://doi.org/10.2210/pdb1W85/pdb

Classification: OXIDOREDUCTASE
Organism(s): Geobacillus stearothermophilus
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2004-09-16 Released: 2004-11-02
Deposition Author(s): Frank, R.A.W., Pratap, J.V., Pei, X.Y., Perham, R.N., Luisi, B.F.

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

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

PubMed: 15514159 Search on PubMed
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.

Macromolecule Content

Total Structure Weight: 319.85 kDa
Atom Count: 23,509
Modelled Residue Count: 2,811
Deposited Residue Count: 2,866
Unique protein chains: 3

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
PYRUVATE DEHYDROGENASE E1 COMPONENT, ALPHA SUBUNIT	A, C, E, G	368	Geobacillus stearothermophilus	Mutation(s): 0 EC: 1.2.4.1
UniProt
Find proteins for P21873 (Geobacillus stearothermophilus) Explore P21873 Go to UniProtKB: P21873
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P21873
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
PYRUVATE DEHYDROGENASE E1 COMPONENT, BETA SUBUNIT	B, D, F, H	324	Geobacillus stearothermophilus	Mutation(s): 0 EC: 1.2.4.1
UniProt
Find proteins for P21874 (Geobacillus stearothermophilus) Explore P21874 Go to UniProtKB: P21874
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P21874
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
DIHYDROLIPOYLLYSINE-RESIDUE ACETYLTRANSFERASE COMPONENT OF PYRUVATE	I, J	49	Geobacillus stearothermophilus	Mutation(s): 0 EC: 2.3.1.12
UniProt
Find proteins for P11961 (Geobacillus stearothermophilus) Explore P11961 Go to UniProtKB: P11961
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P11961
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
TPP Query on TPP Download Ideal Coordinates CCD File SDF format, chain M [auth A] SDF format, chain R [auth C] SDF format, chain U [auth E] SDF format, chain Z [auth G] MOL2 format, chain M [auth A] MOL2 format, chain R [auth C] MOL2 format, chain U [auth E] MOL2 format, chain Z [auth G] mmCIF format, chain M [auth A] mmCIF format, chain R [auth C] mmCIF format, chain U [auth E] mmCIF format, chain Z [auth G]	M [auth A], R [auth C], U [auth E], Z [auth G]	THIAMINE DIPHOSPHATE C₁₂ H₁₉ N₄ O₇ P₂ S AYEKOFBPNLCAJY-UHFFFAOYSA-O		Interactions Focus chain M [auth A] Focus chain R [auth C] Focus chain U [auth E] Focus chain Z [auth G] Interactions & Density Focus chain M [auth A] Focus chain R [auth C] Focus chain U [auth E] Focus chain Z [auth G]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain L [auth A] SDF format, chain Q [auth C] SDF format, chain Y [auth G] MOL2 format, chain L [auth A] MOL2 format, chain Q [auth C] MOL2 format, chain Y [auth G] mmCIF format, chain L [auth A] mmCIF format, chain Q [auth C] mmCIF format, chain Y [auth G]	L [auth A], Q [auth C], Y [auth G]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain L [auth A] Focus chain Q [auth C] Focus chain Y [auth G] Interactions & Density Focus chain L [auth A] Focus chain Q [auth C] Focus chain Y [auth G]
K Query on K Download Ideal Coordinates CCD File SDF format, chain AA [auth H] SDF format, chain N [auth B] SDF format, chain S [auth D] SDF format, chain V [auth F] MOL2 format, chain AA [auth H] MOL2 format, chain N [auth B] MOL2 format, chain S [auth D] MOL2 format, chain V [auth F] mmCIF format, chain AA [auth H] mmCIF format, chain N [auth B] mmCIF format, chain S [auth D] mmCIF format, chain V [auth F]	AA [auth H], N [auth B], S [auth D], V [auth F]	POTASSIUM ION K NPYPAHLBTDXSSS-UHFFFAOYSA-N		Interactions Focus chain AA [auth H] Focus chain N [auth B] Focus chain S [auth D] Focus chain V [auth F] Interactions & Density Focus chain AA [auth H] Focus chain N [auth B] Focus chain S [auth D] Focus chain V [auth F]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain K [auth A] SDF format, chain O [auth B] SDF format, chain P [auth C] SDF format, chain T [auth E] SDF format, chain W [auth F] SDF format, chain X [auth G] MOL2 format, chain K [auth A] MOL2 format, chain O [auth B] MOL2 format, chain P [auth C] MOL2 format, chain T [auth E] MOL2 format, chain W [auth F] MOL2 format, chain X [auth G] mmCIF format, chain K [auth A] mmCIF format, chain O [auth B] mmCIF format, chain P [auth C] mmCIF format, chain T [auth E] mmCIF format, chain W [auth F] mmCIF format, chain X [auth G]	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		Interactions Focus chain K [auth A] Focus chain O [auth B] Focus chain P [auth C] Focus chain T [auth E] Focus chain W [auth F] Focus chain X [auth G] Interactions & Density Focus chain K [auth A] Focus chain O [auth B] Focus chain P [auth C] Focus chain T [auth E] Focus chain W [auth F] Focus chain X [auth G]

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 = 68.27	α = 90
b = 232.33	β = 90.81
c = 91.924	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
DENZO	data reduction
SCALEPACK	data scaling
AMoRE	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2004-11-02

Deposition Author(s):

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