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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1jm6
Original Entry
Title:
Transferase
Compound:
Pyruvate dehydrogenase kinase, isozyme 2
Mutant:
No
UniProt/Swiss-Prot:
Q64536-PDK2_RAT
EC Class:
2.7.1.99
Other CSA Entries:
Overview of all sites for 1jm6
Homologues of 1jm6
Entries for UniProt/Swiss-Prot: Q64536
Entries for EC: 2.7.1.99
Other Databases:
PDB entry: 1jm6
PDBsum entry: 1jm6
UniProt/Swiss-Prot: Q64536
IntEnz entry: 2.7.1.99
Literature Report:
Introduction:
Mitochondrial Pyruvate Dehydrogenase kinase (PDK) regulates the activity of Pyruvate dehydrogenase complex (PDC) by phosphorylating a serine residue at the E1 subunit and thus inactivating it.

Mitochondrial PDK is in a family of serine protein kinases that lacks sequence similarity with all other eukaryotic protein kinase but show similarity with key motifs of prokaryotic histidine protein kinases and a family of eukaryotic ATPases.

In mammals, 4 isozymes of PDK have been found, PDK1, PDK2, PDK3, PDK4. PDK2 is found in many tissues but is low in amount in lung and spleen. It only phosphorylates site 2 and 3 serine residue of the E1 subunit.
Mechanism:
The mechanism is a general base mechanism. Glu243 deprotonates the targeted serine residue of the pyruvate dehydrogenase E1 subunit and promotes its nucleophilic attack on the terminal phosphate of ATP. His239 polarises Glu243 to allow deprotonation. Magnesium ion coordinated to Asp helps in positioning of the ATP and promotes the nucleophilic attack.
Sites:

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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
4601 0
ElectrostaticSubstrate
It interact with ATP to reduce its negative charge for the nucleophilic attack and help in correct positioning of the ATP
Evidence from paper Evidence concerns Evidence type
PubMed ID 11483605 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA1239 247Sidechain
ElectrostaticResidue
It polarises Glu 1243 for deprotonation.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11278487 Current protein Mutagenesis of residue
PubMed ID 11483605 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLUA1243 251Sidechain
Acid/baseSubstrate
A general base to deprotonate the hydroxyl group of the target E1-alpha Serine residue and promotes the nucleophilic attack of the terminal phosphate of ATP
Evidence from paper Evidence concerns Evidence type
PubMed ID 11278487 Current protein Mutagenesis of residue
PubMed ID 11483605 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 11483605 Current protein Conservation of residue
References:
1
Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase.
C. N. Steussy and K. M. Popov and M. M. Bowker-Kinley and R. B. Sloan and R. A. Harris and J. A. Hamilton
J Biol Chem 276, (40) 37443-50, (2001).
11483605
2
An essential role of Glu-243 and His-239 in the phosphotransfer reaction catalyzed by pyruvate dehydrogenase kinase.
A. Tuganova and M. D. Yoder and K. M. Popov
J Biol Chem 276, (21) 17994-9, (2001).
11278487
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