|Activity||Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.,A phosphoprotein + H(2)O = a protein + phosphate.|
|References for Catalytic Mechanism|
|References||Sections||No. of steps in catalysis|
|||Fig.2, Fig.3, p.7088-7091|
|Journal||Proc Natl Acad Sci U S A|
|Authors||Denu JM, Dixon JE|
|Title||A catalytic mechanism for the dual-specific phosphatases.|
|Authors||Hengge AC, Denu JM, Dixon JE|
|Title||Transition-state structures for the native dual-specific phosphatase VHR and D92N and S131A mutants. Contributions to the driving force for catalysis.|
|Comments||X-ray crystallography (2.1 Angstroms)|
|Authors||Yuvaniyama J, Denu JM, Dixon JE, Saper MA|
|Title||Crystal structure of the dual specificity protein phosphatase VHR.|
|Journal||J Biol Chem|
|Authors||Wiland AM, Denu JM, Mourey RJ, Dixon JE|
|Title||Purification and kinetic characterization of the mitogen-activated protein kinase phosphatase rVH6.|
|Journal||J Biol Chem|
|Authors||Kim JH, Shin DY, Han MH, Choi MU|
|Title||Mutational and kinetic evaluation of conserved His-123 in dual specificity protein-tyrosine phosphatase vaccinia H1-related phosphatase: participation of Tyr-78 and Thr-73 residues in tuning the orientation of His-123.|
|Authors||Schumacher MA, Todd JL, Rice AE, Tanner KG, Denu JM|
|Title||Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase.|
|According to the papers  & , Cys124 functions as nucleophile, which attacks the phosphate on a phosphotyrosine to form a thiol-phosphate intermediate, whilst Asp92 serves a role as general acid, protonating the phenolate leaving group in the first step. This intermediate formation is rate-limiting in the reaction mechanism .|
In the second step, the same acidic residue, Asp92, might acts as the general base, which would activate a water molecule by proton abstraction, and the activated water would hydrolyze the thiol-phosphate . In this breakdown of the phosphoenzyme, Ser131 facilitates the hydrolysis, by its hydroxyl group interacting with the catalytic thiol of Cys124 .
Moreover, the residue corresponding to Arg130 seems to be critical for transition-state stabilization . Along with the sidechain of Arg130, mainchain amide groups of loop 125-130 seems to stabilize the phosphate group.
The paper  indicated that the catalytic mechanism of this enzyme involved a highly dissociative transition state (SN1-like reaction), in which bond cleavage and protonation of the leaving group by the acid seem well advanced.