title: Crystal structure of the protein histidine phosphatase SixA in the multistep His-Asp phosphorelay.
abstract: 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 A and 1.90 A resolution, respectively. The results provide the first three-dimensional view of a bacterial protein histidine phosphatase, revealing a compact alpha/beta 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 alpha-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.
authors.affiliation: Structural Biology Laboratory, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hamada
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizuno
authors.forename: Toshio
authors.initials: T
authors.lastname: Hakoshima
mesh_terms: D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D017973:Tungsten Compounds / Q000737:chemistry
chemical_list: D029968:Escherichia coli Proteins; D017973:Tungsten Compounds; D001224:Aspartic Acid; D006639:Histidine; D010749:Phosphoprotein Phosphatases; C503287:SixA protein, E coli; C045951:tungstate