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 A. Harris, Jean A. Hamilton

Research output: Contribution to journalArticle

64 Scopus citations

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

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Steussy, C. N., Popov, K. M., Bowker-Kinley, M. M., Sloan, R. B., Harris, R. A., & 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