Structure of pyruvate dehydrogenase kinase - Novel folding pattern for a serine protein kinase

The structure of mitochondrial pyruvate dehydrogenase kinase isozyme 2 is o f interest because it represents a family of serine-specific protein kinase s 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-Angstrom crystal struct ure 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 b undle of four amphipathic alpha -helices, whereas the C-terminal half is fo lded into an alpha/beta sandwich that contains the nucleotide-binding site. Analysis of the structure reveals this C-terminal domain to be very simila r to the nucleotide-binding domain of bacterial histidine kinases, but the catalytic mechanism appears similar to that of the eukaryotic serine kinase s and ATPases.