title: First structure of a eukaryotic phosphohistidine phosphatase.
abstract: Phosphatases are a diverse group of enzymes that regulate numerous cellular processes. Much of what is known relates to the tyrosine, threonine, and serine phosphatases, whereas the histidine phosphatases have not been studied as much. The structure of phosphohistidine phosphatase (PHPT1), the first identified eukaryotic-protein histidine phosphatase, has been determined to a resolution of 1.9A using multiple-wavelength anomalous dispersion methods. This enzyme can dephosphorylate a variety of proteins (e.g. ATP-citrate lyase and the beta-subunit of G proteins). A putative active site has been identified by its electrostatic character, ion binding, and conserved protein residues. Histidine 53 is proposed to play a major role in histidine dephosphorylation based on these observations and previous mutational studies. Models of peptide binding are discussed to suggest possible mechanisms for substrate recognition.
authors.affiliation: Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Busam
authors.forename: Ann-Gerd
authors.initials: AG
authors.lastname: Thorsell
authors.forename: Alex
authors.initials: A
authors.lastname: Flores
authors.forename: Martin
authors.initials: M
authors.lastname: Hammarström
authors.forename: Camilla
authors.initials: C
authors.lastname: Persson
authors.forename: B Martin
authors.initials: BM
authors.lastname: Hallberg
mesh_terms: D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D006639:Histidine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D008024:Ligands; D011994:Recombinant Proteins; D006639:Histidine; C504019:PHPT1 protein, human; D010744:Phosphoric Monoester Hydrolases; C005436:phosphohistidine