Portal de Periódicos da CAPES

Structure of Pyruvate Dehydrogenase Kinase

2001; Elsevier BV; Volume: 276; Issue: 40 Linguagem: Inglês

10.1074/jbc.m104285200

1083-351X

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

ATP Synthase and ATPases Research

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.