title: The structure of the bovine protein tyrosine phosphatase dimer reveals a potential self-regulation mechanism.
abstract: The bovine protein tyrosine phosphatase (BPTP) is a member of the class of low-molecular weight protein tyrosine phosphatases (PTPases) found to be ubiquitous in mammalian cells. The catalytic site of BPTP contains a CX(5)R(S/T) phosphate-binding motif or P-loop (residues 12-19) which is the signature sequence for all PTPases. Ser19, the final residue of the P-loop motif, interacts with the catalytic Cys12 and participates in stabilizing the conformation of the active site through interactions with Asn15, also in the P-loop. Mutations at Ser19 result in an enzyme with altered kinetic properties with changes in the pK(a) of the neighboring His72. The X-ray structure of the S19A mutant enzyme shows that the general conformation of the P-loop is preserved. However, changes in the loop containing His72 result in a displacement of the His72 side chain that may explain the shift in the pK(a). In addition, it was found that in the crystal, the protein forms a dimer in which Tyr131 and Tyr132 from one monomer insert into the active site of the other monomer, suggesting a dual-tyrosine motif on target sites for this enzyme. Since the activity of this PTPase is reportedly regulated by phosphorylation at Tyr131 and Tyr132, the structure of this dimer may provide a model of a self-regulation mechanism for the low-molecular weight PTPases.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tabernero
authors.forename: B N
authors.initials: BN
authors.lastname: Evans
authors.forename: P A
authors.initials: PA
authors.lastname: Tishmack
authors.forename: R L
authors.initials: RL
authors.lastname: Van Etten
authors.forename: C V
authors.initials: CV
authors.lastname: Stauffacher
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D019281:Dimerization; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism
chemical_list: D012694:Serine; D017027:Protein Tyrosine Phosphatases