An overview of the protein tyrosine phosphatase superfamily.

Wei Qing Wang, Jin Peng Sun, Zhong-Yin Zhang

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The human genome encodes approximately 100 phosphatases that belong to the protein tyrosine phosphatase (PTP) superfamily, whose substrates range from proteins to phosphoinositides and mRNAs. The hallmark for this superfamily is the active site sequence C(X)5R, also known as the PTP signature motif. The PTPs are key regulatory components in signal transduction pathways and the importance of PTPs in the control of cellular signaling is well established. Furthermore, there are compelling reasons to believe that PTP inhibitors may serve as novel medicinal agents for the treatment of various diseases. Based on structure and substrate specificity, the PTP super-family is divided into four distinct subfamilies: 1). pTyr specific PTPs, 2). dual specificity phosphatases, 3). Cdc25 phosphatases, and 4). LMW PTPs. The PTPs have similar core structures made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha loop that encompasses the PTP signature motif. Not surprisingly, they employ a common chemical mechanism for phosphate hydrolysis despite the differences in substrate specificity. Despite the conserved structural and catalytic properties, there are also sufficient differences in the active site pockets and its immediate surrounding environment among different PTPs. Further structural and mechanistic study will continue to be of considerable importance, providing a solid basis for inhibitor design.

Original languageEnglish (US)
Pages (from-to)739-748
Number of pages10
JournalCurrent Topics in Medicinal Chemistry
Volume3
Issue number7
StatePublished - 2003
Externally publishedYes

Fingerprint

Protein Tyrosine Phosphatases
Dual Specificity Phosphatase 3
Substrate Specificity
Catalytic Domain
Substrates
cdc25 Phosphatases
Cell signaling
Signal transduction
Human Genome
Phosphatidylinositols
Phosphoric Monoester Hydrolases
Hydrolysis
Signal Transduction
Genes
Phosphates
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Chemistry(all)

Cite this

An overview of the protein tyrosine phosphatase superfamily. / Wang, Wei Qing; Sun, Jin Peng; Zhang, Zhong-Yin.

In: Current Topics in Medicinal Chemistry, Vol. 3, No. 7, 2003, p. 739-748.

Research output: Contribution to journalArticle

@article{1fb4e8977ce748eab4d6dbc7ec7820a7,
title = "An overview of the protein tyrosine phosphatase superfamily.",
abstract = "The human genome encodes approximately 100 phosphatases that belong to the protein tyrosine phosphatase (PTP) superfamily, whose substrates range from proteins to phosphoinositides and mRNAs. The hallmark for this superfamily is the active site sequence C(X)5R, also known as the PTP signature motif. The PTPs are key regulatory components in signal transduction pathways and the importance of PTPs in the control of cellular signaling is well established. Furthermore, there are compelling reasons to believe that PTP inhibitors may serve as novel medicinal agents for the treatment of various diseases. Based on structure and substrate specificity, the PTP super-family is divided into four distinct subfamilies: 1). pTyr specific PTPs, 2). dual specificity phosphatases, 3). Cdc25 phosphatases, and 4). LMW PTPs. The PTPs have similar core structures made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha loop that encompasses the PTP signature motif. Not surprisingly, they employ a common chemical mechanism for phosphate hydrolysis despite the differences in substrate specificity. Despite the conserved structural and catalytic properties, there are also sufficient differences in the active site pockets and its immediate surrounding environment among different PTPs. Further structural and mechanistic study will continue to be of considerable importance, providing a solid basis for inhibitor design.",
author = "Wang, {Wei Qing} and Sun, {Jin Peng} and Zhong-Yin Zhang",
year = "2003",
language = "English (US)",
volume = "3",
pages = "739--748",
journal = "Current Topics in Medicinal Chemistry",
issn = "1568-0266",
publisher = "Bentham Science Publishers B.V.",
number = "7",

}

TY - JOUR

T1 - An overview of the protein tyrosine phosphatase superfamily.

AU - Wang, Wei Qing

AU - Sun, Jin Peng

AU - Zhang, Zhong-Yin

PY - 2003

Y1 - 2003

N2 - The human genome encodes approximately 100 phosphatases that belong to the protein tyrosine phosphatase (PTP) superfamily, whose substrates range from proteins to phosphoinositides and mRNAs. The hallmark for this superfamily is the active site sequence C(X)5R, also known as the PTP signature motif. The PTPs are key regulatory components in signal transduction pathways and the importance of PTPs in the control of cellular signaling is well established. Furthermore, there are compelling reasons to believe that PTP inhibitors may serve as novel medicinal agents for the treatment of various diseases. Based on structure and substrate specificity, the PTP super-family is divided into four distinct subfamilies: 1). pTyr specific PTPs, 2). dual specificity phosphatases, 3). Cdc25 phosphatases, and 4). LMW PTPs. The PTPs have similar core structures made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha loop that encompasses the PTP signature motif. Not surprisingly, they employ a common chemical mechanism for phosphate hydrolysis despite the differences in substrate specificity. Despite the conserved structural and catalytic properties, there are also sufficient differences in the active site pockets and its immediate surrounding environment among different PTPs. Further structural and mechanistic study will continue to be of considerable importance, providing a solid basis for inhibitor design.

AB - The human genome encodes approximately 100 phosphatases that belong to the protein tyrosine phosphatase (PTP) superfamily, whose substrates range from proteins to phosphoinositides and mRNAs. The hallmark for this superfamily is the active site sequence C(X)5R, also known as the PTP signature motif. The PTPs are key regulatory components in signal transduction pathways and the importance of PTPs in the control of cellular signaling is well established. Furthermore, there are compelling reasons to believe that PTP inhibitors may serve as novel medicinal agents for the treatment of various diseases. Based on structure and substrate specificity, the PTP super-family is divided into four distinct subfamilies: 1). pTyr specific PTPs, 2). dual specificity phosphatases, 3). Cdc25 phosphatases, and 4). LMW PTPs. The PTPs have similar core structures made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha loop that encompasses the PTP signature motif. Not surprisingly, they employ a common chemical mechanism for phosphate hydrolysis despite the differences in substrate specificity. Despite the conserved structural and catalytic properties, there are also sufficient differences in the active site pockets and its immediate surrounding environment among different PTPs. Further structural and mechanistic study will continue to be of considerable importance, providing a solid basis for inhibitor design.

UR - http://www.scopus.com/inward/record.url?scp=0037647196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037647196&partnerID=8YFLogxK

M3 - Article

C2 - 12678841

AN - SCOPUS:0037647196

VL - 3

SP - 739

EP - 748

JO - Current Topics in Medicinal Chemistry

JF - Current Topics in Medicinal Chemistry

SN - 1568-0266

IS - 7

ER -