title: Revisiting histidine-dependent acid phosphatases: a distinct group of tyrosine phosphatases.
abstract: Although classical protein tyrosine phosphatase (PTP) superfamily members are cysteine-dependent, emerging evidence shows that many acid phosphatases (AcPs) function as histidine-dependent PTPs in vivo. These AcPs dephosphorylate phospho-tyrosine substrates intracellularly and could have roles in development and disease. In contrast to cysteine-dependent PTPs, they utilize histidine, rather than cysteine, for substrate dephosphorylation. Structural analyses reveal that active site histidine, but not cysteine, faces towards the substrate and functions as the phosphate acceptor. Nonetheless, during dephosphorylation, both histidine-dependent and cysteine-dependent PTPs use their active site arginine and aspartate for substrate binding and proton donation, respectively. Thus, we propose that they should be referred to as a distinct group of 'histidine-dependent PTPs' within the PTP superfamily.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Veeramani
authors.forename: Ming-Shyue
authors.initials: MS
authors.lastname: Lee
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Lin
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D020134:Catalytic Domain; D003545:Cysteine / Q000737:chemistry; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry; D010802:Phylogeny; D010944:Plants / Q000378:metabolism; D011487:Protein Conformation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology*; D013045:Species Specificity
chemical_list: D010710:Phosphates; D006639:Histidine; D000135:Acid Phosphatase; D017027:Protein Tyrosine Phosphatases; D003545:Cysteine