3CRK

Crystal structure of the PDHK2-L2 complex.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural and functional insights into the molecular mechanisms responsible for the regulation of pyruvate dehydrogenase kinase 2.

Green, T.Grigorian, A.Klyuyeva, A.Tuganova, A.Luo, M.Popov, K.M.

(2008) J Biol Chem 283: 15789-15798

  • DOI: https://doi.org/10.1074/jbc.M800311200
  • Primary Citation of Related Structures:  
    3CRK, 3CRL

  • PubMed Abstract: 

    PDHK2 is a mitochondrial protein kinase that phosphorylates pyruvate dehydrogenase complex, thereby down-regulating the oxidation of pyruvate. Here, we present the crystal structure of PDHK2 bound to the inner lipoyl-bearing domain of dihydrolipoamide transacetylase (L2) determined with or without bound adenylyl imidodiphosphate. Both structures reveal a PDHK2 dimer complexed with two L2 domains. Comparison with apo-PDHK2 shows that L2 binding causes rearrangements in PDHK2 structure that affect the L2- and E1-binding sites. Significant differences are found between PDHK2 and PDHK3 with respect to the structure of their lipoyllysine-binding cavities, providing the first structural support to a number of studies showing that these isozymes are markedly different with respect to their affinity for the L2 domain. Both structures display a novel type II potassium-binding site located on the PDHK2 interface with the L2 domain. Binding of potassium ion at this site rigidifies the interface and appears to be critical in determining the strength of L2 binding. Evidence is also presented that potassium ions are indispensable for the cross-talk between the nucleotide- and L2-binding sites of PDHK2. The latter is believed to be essential for the movement of PDHK2 along the surface of the transacetylase scaffold.


  • Organizational Affiliation

    Department of Microbiology, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Pyruvate dehydrogenase [lipoamide] kinase isozyme 2, mitochondrial
A, B
407Rattus norvegicusMutation(s): 0 
Gene Names: Pdk2
EC: 2.7.11.2
UniProt
Find proteins for Q64536 (Rattus norvegicus)
Explore Q64536 
Go to UniProtKB:  Q64536
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ64536
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
C, D
87Homo sapiensMutation(s): 0 
Gene Names: DLATDLTA
EC: 2.3.1.12
UniProt & NIH Common Fund Data Resources
Find proteins for P10515 (Homo sapiens)
Explore P10515 
Go to UniProtKB:  P10515
PHAROS:  P10515
GTEx:  ENSG00000150768 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10515
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
LA2
Query on LA2
C, D
L-PEPTIDE LINKINGC14 H28 N2 O3 S2LYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.38α = 90
b = 120.679β = 96.03
c = 71.466γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
COMOphasing
REFMACrefinement
PDB_EXTRACTdata extraction
MAR345data collection
HKL-2000data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description