Crystal structure of the protein histidine phosphatase SixA in the multistep His-Asp phosphorelay

Keisuke Hamda, Masato Kato, Toshiyuki Shimizu, Kentaro Ihara, Takeshi Mizuno, Toshio Hakoshima

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The multiple histidine-aspartate phosphorelay system plays a crucial role in cellular adaptation to environments in microorganisms and plants. Like kinase-phosphatase systems in higher eukaryotes, the multiple steps provide additional regulatory checkpoints with phosphatases. The Escherichia coli phosphatase SixA exhibits protein phosphatase activity against the histidine-containing phosphotransfer (HPt) domain located in the C-terminus of the histidine kinase ArcB engaged in anaerobic responses. We have determined the crystal structures of the free and tungstate-bound forms of SixA at 2.06 Å and 1.90 Å resolution, respectively. The results provide the first three-dimensional view of a bacterial protein histidine phosphatase, revealing a compact α/β architecture related to a family of phosphatases containing the arginine-histidine-glycine (RHG) motif at their active sites. Compared with these RHG phosphatases, SixA lacks an extra α-helical subdomain as a lid over the active site, thereby forming a relatively shallow groove important for the accommodation of the HPt domain of ArcB. The tungstate ion, which mimics the substrate phosphate group, is located at the centre of the active site where the active residue, His8, points to the tungsten atom in the mode of in-line nucleophilic attack.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalGenes to Cells
Issue number1
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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