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PDBsum entry 1gjv

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protein ligands metals links
Transferase PDB id
1gjv
Jmol
Contents
Protein chain
314 a.a. *
Ligands
AGS
Metals
_CL ×5
_MG
__K
Waters ×70
* Residue conservation analysis
PDB id:
1gjv
Name: Transferase
Title: Branched-chain alpha-ketoacid dehydrogenase kinase (bck) complxed with atp-gamma-s
Structure: [3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase. Chain: a. Synonym: branched-chain alpha-ketoacid dehydrogenase kinase. Engineered: yes. Other_details: c-terminal his6-tag
Source: Rattus norvegicus. Rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Monomer (from PDB file)
Resolution:
2.70Å     R-factor:   0.218     R-free:   0.269
Authors: M.Machius,J.L.Chuang,M.R.Wynn,D.R.Tomchick,D.T.Chuang
Key ref:
M.Machius et al. (2001). Structure of rat BCKD kinase: nucleotide-induced domain communication in a mitochondrial protein kinase. Proc Natl Acad Sci U S A, 98, 11218-11223. PubMed id: 11562470 DOI: 10.1073/pnas.201220098
Date:
03-Aug-01     Release date:   11-Oct-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q00972  (BCKD_RAT) -  [3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial
Seq:
Struc:
412 a.a.
314 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.4  - [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] = ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
ATP
Bound ligand (Het Group name = AGS)
matches with 93.75% similarity
+ [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]
= ADP
+ [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   3 terms 
  Biological process     phosphorylation   3 terms 
  Biochemical function     nucleotide binding     8 terms  

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.201220098 Proc Natl Acad Sci U S A 98:11218-11223 (2001)
PubMed id: 11562470  
 
 
Structure of rat BCKD kinase: nucleotide-induced domain communication in a mitochondrial protein kinase.
M.Machius, J.L.Chuang, R.M.Wynn, D.R.Tomchick, D.T.Chuang.
 
  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.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. The mammalian protein kinase BCK. (A) Overall view of the rat BCK dimer with the phosphotransfer reaction product ADP shown as ball-and-stick model. Strands in the K domain are not labeled. (B) Same as A, but rotated 90° around the horizontal line. All figures were made with BOBSCRIPT (46) and POVRAY (www.povray.org). (C) Sequence alignment of mitochondrial protein kinases. Similar residues are colored (yellow, hydrophobic; blue, basic; red, acidic; green, others). Residues observed in the rat BCK structure are depicted below the sequences (red, helices; blue, strands; gray, others); the conserved nucleotide-binding motifs are indicated above the consensus sequence. (D) Residues in the rat BCK dimer interface. Water molecules participate in dimer formation only at the periphery, but not in the core.
Figure 2.
Fig. 2. Comparison of BCK with structurally related kinases and ATPases. (A) Nucleotide-binding domain. BCK with ADP, CheA "empty" (PDB ID code 1B3Q), and MutL with ADPNP (PDB ID code 1B63). (B) B domain. BCK, CheA-HPt (PDB ID code 1i5n), ArcB (PDB ID code 1A0B), and Ypd1p (PDB ID code 1C02).
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19960440 M.Karlsson, P.R.Jensen, R.in 't Zandt, A.Gisselsson, G.Hansson, J...Duus, S.Meier, and M.H.Lerche (2010).
Imaging of branched chain amino acid metabolism in tumors with hyperpolarized 13C ketoisocaproate.
  Int J Cancer, 127, 729-736.  
19420697 K.Akita, Y.Fujimura, G.Bajotto, and Y.Shimomura (2009).
Inhibition of branched-chain alpha-ketoacid dehydrogenase kinase by thiamine pyrophosphate at different potassium ionic levels.
  Biosci Biotechnol Biochem, 73, 1189-1191.  
18658136 R.M.Wynn, M.Kato, J.L.Chuang, S.C.Tso, J.Li, and D.T.Chuang (2008).
Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity.
  J Biol Chem, 283, 25305-25315.
PDB codes: 2zkj 3d2r
18387944 T.Green, A.Grigorian, A.Klyuyeva, A.Tuganova, M.Luo, and K.M.Popov (2008).
Structural and functional insights into the molecular mechanisms responsible for the regulation of pyruvate dehydrogenase kinase 2.
  J Biol Chem, 283, 15789-15798.
PDB codes: 3crk 3crl
17586771 J.J.Petkowski, M.Chruszcz, M.D.Zimmerman, H.Zheng, T.Skarina, O.Onopriyenko, M.T.Cymborowski, K.D.Koclega, A.Savchenko, A.Edwards, and W.Minor (2007).
Crystal structures of TM0549 and NE1324--two orthologs of E. coli AHAS isozyme III small regulatory subunit.
  Protein Sci, 16, 1360-1367.
PDB codes: 2fgc 2pc6
17683942 M.Kato, J.Li, J.L.Chuang, and D.T.Chuang (2007).
Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol.
  Structure, 15, 992.
PDB codes: 2q8f 2q8g 2q8h 2q8i
15861126 M.Kato, J.L.Chuang, S.C.Tso, R.M.Wynn, and D.T.Chuang (2005).
Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex.
  EMBO J, 24, 1763-1774.
PDB codes: 1y8n 1y8o 1y8p
15229886 N.Fernandez-Fuentes, A.Hermoso, J.Espadaler, E.Querol, F.X.Aviles, and B.Oliva (2004).
Classification of common functional loops of kinase super-families.
  Proteins, 56, 539-555.  
15491368 R.Hõrak, H.Ilves, P.Pruunsild, M.Kuljus, and M.Kivisaar (2004).
The ColR-ColS two-component signal transduction system is involved in regulation of Tn4652 transposition in Pseudomonas putida under starvation conditions.
  Mol Microbiol, 54, 795-807.  
15576032 R.M.Wynn, M.Kato, M.Machius, J.L.Chuang, J.Li, D.R.Tomchick, and D.T.Chuang (2004).
Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation.
  Structure, 12, 2185-2196.
PDB codes: 1u5b 1x7w 1x7x 1x7y 1x7z 1x80
12631265 T.E.Roche, Y.Hiromasa, A.Turkan, X.Gong, T.Peng, X.Yan, S.A.Kasten, H.Bao, and J.Dong (2003).
Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1.
  Eur J Biochem, 270, 1050-1056.  
11900524 E.Tan, P.G.Besant, and P.V.Attwood (2002).
Mammalian histidine kinases: do they REALLY exist?
  Biochemistry, 41, 3843-3851.  
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.