Branched-chain 6-ketoacid dehydrogenase kinase: A mammalian enzyme with histidine kinase activity.

Whereas phosphoesters of serine, threonine, and tyrosine are present in great abundance in mammalian cells, only limited information is available for other amino acids modified by a phosphate group. Phosphohistidine in proteins has been discovered in mammalian cells, but no enzyme with histidine kinase activity has been reported to date. The present study demonstrates for the first time the histidine kinase activity of a mammalian protein. Branched-chain alpha-ketoacid dehydrogenase kinase, a mitochondrial enzyme, has high sequence similarity with histidine kinases from lower organisms but has been classified as a serine/threonine kinase. Our studies indicate that in addition to a serine this enzyme also autophosphorylates a histidine residue. This finding suggests that histidine kinases are not restricted to lower organisms.