1GJV

Branched-chain alpha-ketoacid dehydrogenase kinase (BCK) complxed with ATP-gamma-S


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.218 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structure of Rat Bckd Kinase: Nucleotide-Induced Domain Communication in a Mitochondrial Protein Kinase.

Machius, M.Chuang, J.L.Wynn, M.R.Tomchick, D.R.Chuang, D.T.

(2001) Proc Natl Acad Sci U S A 98: 11218

  • DOI: https://doi.org/10.1073/pnas.201220098
  • Primary Citation of Related Structures:  
    1GJV, 1GKX, 1GKZ

  • PubMed Abstract: 

    Mitochondrial protein kinases (mPKs) are molecular switches that down-regulate the oxidation of branched-chain alpha-ketoacids and pyruvate. Elevated levels of these metabolites are implicated in disease states such as insulin-resistant Type II diabetes, branched-chain ketoaciduria, and primary lactic acidosis. We report a three-dimensional structure of a member of the mPK family, rat branched-chain alpha-ketoacid dehydrogenase kinase (BCK). BCK features a characteristic nucleotide-binding domain and a four-helix bundle domain. These two domains are reminiscent of modules found in protein histidine kinases (PHKs), which are involved in two-component signal transduction systems. Unlike PHKs, BCK dimerizes through direct interaction of two opposing nucleotide-binding domains. Nucleotide binding to BCK is uniquely mediated by both potassium and magnesium. Binding of ATP induces disorder-order transitions in a loop region at the nucleotide-binding site. These structural changes lead to the formation of a quadruple aromatic stack in the interface between the nucleotide-binding domain and the four-helix bundle domain, where they induce a movement of the top portion of two helices. Phosphotransfer induces further ordering of the loop region, effectively trapping the reaction product ADP, which explains product inhibition in mPKs. The BCK structure is a prototype for all mPKs and will provide a framework for structure-assisted inhibitor design for this family of kinases.


  • Organizational Affiliation

    Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA. Mischa.Machius@UTSouthwestern.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
[3-METHYL-2-OXOBUTANOATE DEHYDROGENASE [LIPOAMIDE]] KINASE388Rattus norvegicusMutation(s): 0 
EC: 2.7.1.115
UniProt
Find proteins for Q00972 (Rattus norvegicus)
Explore Q00972 
Go to UniProtKB:  Q00972
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ00972
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
AGS
Query on AGS

Download Ideal Coordinates CCD File 
I [auth A]PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER
C10 H16 N5 O12 P3 S
NLTUCYMLOPLUHL-KQYNXXCUSA-N
K
Query on K

Download Ideal Coordinates CCD File 
F [auth A]POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A],
D [auth A],
G [auth A],
H [auth A]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
MG
Query on MG

Download Ideal Coordinates CCD File 
E [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.218 
  • Space Group: P 42 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 127.722α = 90
b = 127.722β = 90
c = 74.314γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-10-11
    Type: Initial release
  • Version 1.1: 2013-01-30
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Other, Structure summary, Version format compliance
  • Version 1.2: 2019-03-06
    Changes: Data collection, Experimental preparation, Other
  • Version 1.3: 2019-05-15
    Changes: Data collection, Experimental preparation