spacer
View the latest EBI news stories and important announcements...
more

spacer
Search The CSA
PDB ID
UNIPROT ID
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1jm6

E.C. name[pyruvate dehydrogenase (acetyl-transferring)] kinase
SpeciesRattus norvegicus (Rat)
E.C. Number (IntEnz) 2.7.11.2
CSA Homologues of 1jm6There are 24 Homologs
CSA Entries With UniProtID Q64536
CSA Entries With EC Number 2.7.11.2
PDBe Entry 1jm6
PDBSum Entry 1jm6
MACiE Entry 1jm6

Literature Report

IntroductionMitochondrial 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.
MechansimThe 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.
Reaction

Catalytic Sites for 1jm6

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA1239247macie:sideChainIt polarises Glu 1243 for deprotonation.
GluA1243251macie:sideChainA 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

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB1239247macie:sideChainIt polarises Glu 1243 for deprotonation.
GluB1243251macie:sideChainA 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

Literature References

Notes:
Steussy CN
Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase.
J Biol Chem 2001 276 37443-37450
PubMed: 11483605
Tuganova A
An essential role of Glu-243 and His-239 in the phosphotransfer reaction catalyzed by pyruvate dehydrogenase kinase.
J Biol Chem 2001 276 17994-17999
PubMed: 11278487
spacer
spacer