The active site specificity of the Yersinia protein-tyrosine phosphatase

Derek Dunn, Li Chen, David S. Lawrence, Zhong-Yin Zhang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Yersinia protein-tyrosine phosphatase substrates have been synthesized employing an expedient methodology that incorporates phosphorylated non- amino acid residues into an active site-directed peptide. While the peptidic portion of these compounds serves an enzyme targeting role, the nonpeptidic component provides a critical assessment of the range of functionality that can he accommodated within the active site region. We have found that the Yersinia phosphatase hydrolyzes both L- and D-stereoisomers of phosphotyrosine in active site-directed peptides, with the former serving as a 10-fold more efficient substrate than the latter. In addition, this enzyme catalyzes the hydrolysis of a variety of aromatic and aliphatic phosphates. Indeed, a peptide bearing the achiral phosphotyrosine analog, phosphotyramine, is not only the most efficient substrate described in this study, it is also one of the most efficient substrates ever reported for the Yersinia phosphatase. Straight chain peptide-bound aliphatic phosphates of the general structure, (Glu)4-NH-(CH2)(n)-OPO3/2- (n = 2-8), are also hydrolyzed, where the most efficient substrate contains seven methylene groups. Finally, a comparison of the substrate efficacy of the peptide-bound species with that of the corresponding non-peptidic analogs, reveals that the peptide component enhances k(cat)/K(m) by up to nearly 3 orders of magnitude.

Original languageEnglish (US)
Pages (from-to)168-173
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number1
DOIs
StatePublished - Jan 5 1996
Externally publishedYes

Fingerprint

Yersinia
Protein Tyrosine Phosphatases
Catalytic Domain
Peptides
Substrates
Phosphotyrosine
Phosphoric Monoester Hydrolases
Bearings (structural)
Phosphates
Stereoisomerism
Enzymes
Hydrolysis
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

The active site specificity of the Yersinia protein-tyrosine phosphatase. / Dunn, Derek; Chen, Li; Lawrence, David S.; Zhang, Zhong-Yin.

In: Journal of Biological Chemistry, Vol. 271, No. 1, 05.01.1996, p. 168-173.

Research output: Contribution to journalArticle

Dunn, Derek ; Chen, Li ; Lawrence, David S. ; Zhang, Zhong-Yin. / The active site specificity of the Yersinia protein-tyrosine phosphatase. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 1. pp. 168-173.
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