1C0E

Active Site S19A Mutant of Bovine Heart Phosphotyrosyl Phosphatase

Summary for 1C0E

• Entry DOI: 10.2210/pdb1c0e/pdb
• Related: 1PNT 5PNT
• Descriptor: PROTEIN (TYROSINE PHOSPHATASE (ORTHOPHOSPHORIC MONOESTER PHOSPHOHYDROLASE)), PHOSPHATE ION (3 entities in total)
• Functional Keywords: tyrosine phosphatase, phosphatase dimer, hydrolase
• Biological source: Bos taurus (cattle)
• Cellular location: Cytoplasm: P11064
• Total number of polymer chains: 2
• Total formula weight: 36050.59

Authors

Tabernero, L.,Evans, B.N.,Tishmack, P.A.,Van Etten, R.L.,Stauffacher, C.V. (deposition date: 1999-07-15, release date: 1999-09-28, Last modification date: 2024-02-07)

Primary citation

Tabernero, L.,Evans, B.N.,Tishmack, P.A.,Van Etten, R.L.,Stauffacher, C.V.
The structure of the bovine protein tyrosine phosphatase dimer reveals a potential self-regulation mechanism.
Biochemistry, 38:11651-11658, 1999

PubMed 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.

PubMed: 10512620
DOI: 10.1021/bi990381x

Experimental method

X-RAY DIFFRACTION (2.2 Å)