Document Type

Article

Journal Title

Trends in biochemical sciences

Publication Date

6-2009

Volume

34

Abstract

Although classical protein tyrosine phosphatase (PTP) superfamily members are cysteine-dependent, emerging evidence shows that many acid phosphatases (AcPs) function as histidine-dependent PTPs in vivo. These AcPs dephosphorylate phospho-tyrosine substrates intracellularly and could have roles in development and disease. In contrast to cysteine-dependent PTPs, they utilize histidine, rather than cysteine, for substrate dephosphorylation. Structural analyses reveal that active site histidine, but not cysteine, faces towards the substrate and functions as the phosphate acceptor. Nonetheless, during dephosphorylation, both histidine-dependent and cysteine-dependent PTPs use their active site arginine and aspartate for substrate binding and proton donation, respectively. Thus, we propose that they should be referred to as a distinct group of 'histidine-dependent PTPs' within the PTP superfamily.

MeSH Headings

Acid Phosphatase, Animals, Catalytic Domain, Cysteine, Histidine, Humans, Models, Biological, Neurons, Phosphates, Phylogeny, Plants, Protein Conformation, Protein Tyrosine Phosphatases, Species Specificity

ISSN

0968-0004

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Trends in Biochemical Sciences. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Trends in Biochemical Sciences, [34, 6, (2009)] DOI#10.1016/j.tibs.2009.03.00

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