Structure of pyruvate dehydrogenase kinase

Novel folding pattern for a serine protein kinase

C. Nicklaus Steussy, Kirill M. Popov, Melissa M. Bowker-Kinley, Robert B. Sloan, Robert Harris, Jean A. Hamilton

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The structure of mitochondrial pyruvate dehydrogenase kinase isozyme 2 is of interest because it represents a family of serine-specific protein kinases that lack sequence similarity with all other eukaryotic protein kinases. Similarity exists instead with key motifs of prokaryotic histidine protein kinases and a family of eukaryotic ATPases. The 2.5-Å crystal structure reported here reveals that pyruvate dehydrogenase kinase isozyme 2 has two domains of about the same size. The N-terminal half is dominated by a bundle of four amphipathic α-helices, whereas the C-terminal half is folded into an α/β sandwich that contains the nucleotide-binding site. Analysis of the structure reveals this C-terminal domain to be very similar to the nucleotide-binding domain of bacterial histidine kinases, but the catalytic mechanism appears similar to that of the eukaryotic serine kinases and ATPases.

Original languageEnglish
Pages (from-to)37443-37450
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number40
DOIs
StatePublished - Oct 5 2001

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Protein-Serine-Threonine Kinases
Protein Kinases
Adenosine Triphosphatases
Nucleotides
Histidine
Binding Sites
Serine
Phosphotransferases
Crystal structure
pyruvate dehydrogenase (acetyl-transferring) kinase
Histidine Kinase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Steussy, C. N., Popov, K. M., Bowker-Kinley, M. M., Sloan, R. B., Harris, R., & Hamilton, J. A. (2001). Structure of pyruvate dehydrogenase kinase: Novel folding pattern for a serine protein kinase. Journal of Biological Chemistry, 276(40), 37443-37450. https://doi.org/10.1074/jbc.M104285200

Structure of pyruvate dehydrogenase kinase : Novel folding pattern for a serine protein kinase. / Steussy, C. Nicklaus; Popov, Kirill M.; Bowker-Kinley, Melissa M.; Sloan, Robert B.; Harris, Robert; Hamilton, Jean A.

In: Journal of Biological Chemistry, Vol. 276, No. 40, 05.10.2001, p. 37443-37450.

Research output: Contribution to journalArticle

Steussy, C. Nicklaus ; Popov, Kirill M. ; Bowker-Kinley, Melissa M. ; Sloan, Robert B. ; Harris, Robert ; Hamilton, Jean A. / Structure of pyruvate dehydrogenase kinase : Novel folding pattern for a serine protein kinase. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 40. pp. 37443-37450.
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