Comparative kinetic analysis and substrate specificity of the tandem catalytic domains of the receptor-like protein-tyrosine phosphatase α

Li Wu, Arjan Buist, Jeroen Den Hertog, Zhong-Yin Zhang

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The catalytic activity and substrate specificity of protein-tyrosine phosphatase α (PTPα) is primarily controlled by the membrane proximal catalytic domain (D1). The membrane distal (D2) domain of PTPα by itself is a genuine PTPase, possessing catalytic activity comparable to that of D1 using aryl phosphates as substrates. Surprisingly, k(cat) and k(cat)/K(m) for the D2-catalyzed hydrolysis of phosphotyrosine-containing peptides are several orders of magnitude reduced in comparison with those of D1. Substitution of the putative general acid/base Glu-690 in D2 by an Asp, which is invariably found in the WPD motifs in all cytoplasmic PTPases and all the D1 domains of receptor-like PTPases, only increases the k(cat) for D2 by 4- fold. Thus the much reduced D2 activity toward peptide substrates may be due to structural differences in the active sites other than the general acid/base. Alternatively, the D2 domain may have a functional active site with a highly stringent substrate specificity. PTPα display modest peptide substrate selectivity and are sensitive to charges adjacent to phosphotyrosine. In the sequence context of DADEpYLIPQQG (where pY stands for phosphotyrosine), the minimal sizes recognized by PTPα are either ADEpYLI or DADEpY-NH2.

Original languageEnglish (US)
Pages (from-to)6994-7002
Number of pages9
JournalJournal of Biological Chemistry
Volume272
Issue number11
DOIs
StatePublished - Mar 14 1997
Externally publishedYes

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Receptor-Like Protein Tyrosine Phosphatases
Protein Tyrosine Phosphatases
Substrate Specificity
Catalytic Domain
Phosphotyrosine
Kinetics
Substrates
Peptides
Catalyst activity
Membranes
Acids
Viperidae
Hydrolysis
Substitution reactions
Phosphates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Comparative kinetic analysis and substrate specificity of the tandem catalytic domains of the receptor-like protein-tyrosine phosphatase α. / Wu, Li; Buist, Arjan; Den Hertog, Jeroen; Zhang, Zhong-Yin.

In: Journal of Biological Chemistry, Vol. 272, No. 11, 14.03.1997, p. 6994-7002.

Research output: Contribution to journalArticle

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