Chapter 11 - Histidine Kinases: Extended Relationship with GHL ATPases

Abstract

Histidine kinases (HK) share conserved amino acid sequence motifs with members of the DNA topoisomerase II family, the hsp90 family, and the MutL DNA mismatch repair protein family. The three-dimensional structures of a fragment of Hspg0, MutL, and EnvZ, and CheA histidine kinase, which contain the identified conserved sequence motifs, were determined by either X-ray crystallography or nuclear magnetic resonance (NMR). The location of these conserved sequence motifs is topologically similar among these three structures and DNA gyrase. These sequence motifs have been confirmed to form a nucleotide-binding pocket. As DNA gyrase, hsp90, and MutL hydrolyze ATE, they are collectively called the GHL ATPase family . Although histidine kinases do not hydrolyze ATE, they contain an ATP-binding site similar to those of the GHL ATPases and use ATP to phosphorylate a histidine side chain. Most ATPases known to date contain a conserved sequence motif, GXXXXXGKS/T, known as the Walker A motif. Such a sequence motif is absent in GHL ATPases. Similarly, histidine kinases lack typical sequence motifs found in the majority of Ser/Thr and Tyr kinases.