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The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance.

Robson SC, Sévigny J, Zimmermann H - Purinergic Signal. (2006)

Bottom Line: The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtype-specific antibodies have resulted in considerable insights into enzyme structure and function.These advances also allow definition of physiological and patho-physiological implications of NTPDases in a considerable variety of tissues.Biological actions of NTPDases are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides and consequent effects on P2-receptor signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

ABSTRACT
Ectonucleotidases are ectoenzymes that hydrolyze extracellular nucleotides to the respective nucleosides. Within the past decade, ectonucleotidases belonging to several enzyme families have been discovered, cloned and characterized. In this article, we specifically address the cell surface-located members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) family (NTPDase1,2,3, and 8). The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtype-specific antibodies have resulted in considerable insights into enzyme structure and function. These advances also allow definition of physiological and patho-physiological implications of NTPDases in a considerable variety of tissues. Biological actions of NTPDases are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides and consequent effects on P2-receptor signaling. It further appears that the spatial and temporal expression of NTPDases by various cell types within the vasculature, the nervous tissues and other tissues impacts on several patho-physiological processes. Examples include acute effects on cellular metabolism, adhesion, activation and migration with other protracted impacts upon developmental responses, inclusive of cellular proliferation, differentiation and apoptosis, as seen with atherosclerosis, degenerative neurological diseases and immune rejection of transplanted organs and cells. Future clinical applications are expected to involve the development of new therapeutic strategies for transplantation and various inflammatory cardiovascular, gastrointestinal and neurological diseases.

No MeSH data available.


Related in: MedlinePlus

Hypothetical phylogenetic tree derived for 22 selected members of the E-NTPDase family (NTPDase1 to NTPDase8) from rat (r), human (h) and mouse (m), following alignment of amino acid sequences. The length of the lines indicates the differences between amino acid sequences. The graph depicts a clear separation between surface-located (top) and intracellular (bottom) NTPDases. In addition, the major substrate preferences of individual subtypes and the predicted membrane topography for each group of enzymes is given (one or two transmembrane domains, indicated by barrels). Modified from [59].
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Fig1: Hypothetical phylogenetic tree derived for 22 selected members of the E-NTPDase family (NTPDase1 to NTPDase8) from rat (r), human (h) and mouse (m), following alignment of amino acid sequences. The length of the lines indicates the differences between amino acid sequences. The graph depicts a clear separation between surface-located (top) and intracellular (bottom) NTPDases. In addition, the major substrate preferences of individual subtypes and the predicted membrane topography for each group of enzymes is given (one or two transmembrane domains, indicated by barrels). Modified from [59].

Mentions: Eight different ENTPD genes (Table 1 and Fig. 1) encode members of the NTPDase protein family. Four of the NTPDases are typical cell surface-located enzymes with an extracellularly facing catalytic site (NTPDase1, 2, 3, 8). NTPDases 5 and 6 exhibit intracellular localization and undergo secretion after heterologous expression. NTPDases 4 and 7 are entirely intracellularly located, facing the lumen of cytoplasmic organelles (Fig. 1). The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtypespecific antibodies have not only led to considerable insight into enzyme structure and function. These advances have also defined physiological and pathophysiological functions of NTPDases in a considerable variety of tissues.Table 1


The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance.

Robson SC, Sévigny J, Zimmermann H - Purinergic Signal. (2006)

Hypothetical phylogenetic tree derived for 22 selected members of the E-NTPDase family (NTPDase1 to NTPDase8) from rat (r), human (h) and mouse (m), following alignment of amino acid sequences. The length of the lines indicates the differences between amino acid sequences. The graph depicts a clear separation between surface-located (top) and intracellular (bottom) NTPDases. In addition, the major substrate preferences of individual subtypes and the predicted membrane topography for each group of enzymes is given (one or two transmembrane domains, indicated by barrels). Modified from [59].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2254478&req=5

Fig1: Hypothetical phylogenetic tree derived for 22 selected members of the E-NTPDase family (NTPDase1 to NTPDase8) from rat (r), human (h) and mouse (m), following alignment of amino acid sequences. The length of the lines indicates the differences between amino acid sequences. The graph depicts a clear separation between surface-located (top) and intracellular (bottom) NTPDases. In addition, the major substrate preferences of individual subtypes and the predicted membrane topography for each group of enzymes is given (one or two transmembrane domains, indicated by barrels). Modified from [59].
Mentions: Eight different ENTPD genes (Table 1 and Fig. 1) encode members of the NTPDase protein family. Four of the NTPDases are typical cell surface-located enzymes with an extracellularly facing catalytic site (NTPDase1, 2, 3, 8). NTPDases 5 and 6 exhibit intracellular localization and undergo secretion after heterologous expression. NTPDases 4 and 7 are entirely intracellularly located, facing the lumen of cytoplasmic organelles (Fig. 1). The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtypespecific antibodies have not only led to considerable insight into enzyme structure and function. These advances have also defined physiological and pathophysiological functions of NTPDases in a considerable variety of tissues.Table 1

Bottom Line: The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtype-specific antibodies have resulted in considerable insights into enzyme structure and function.These advances also allow definition of physiological and patho-physiological implications of NTPDases in a considerable variety of tissues.Biological actions of NTPDases are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides and consequent effects on P2-receptor signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

ABSTRACT
Ectonucleotidases are ectoenzymes that hydrolyze extracellular nucleotides to the respective nucleosides. Within the past decade, ectonucleotidases belonging to several enzyme families have been discovered, cloned and characterized. In this article, we specifically address the cell surface-located members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) family (NTPDase1,2,3, and 8). The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtype-specific antibodies have resulted in considerable insights into enzyme structure and function. These advances also allow definition of physiological and patho-physiological implications of NTPDases in a considerable variety of tissues. Biological actions of NTPDases are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides and consequent effects on P2-receptor signaling. It further appears that the spatial and temporal expression of NTPDases by various cell types within the vasculature, the nervous tissues and other tissues impacts on several patho-physiological processes. Examples include acute effects on cellular metabolism, adhesion, activation and migration with other protracted impacts upon developmental responses, inclusive of cellular proliferation, differentiation and apoptosis, as seen with atherosclerosis, degenerative neurological diseases and immune rejection of transplanted organs and cells. Future clinical applications are expected to involve the development of new therapeutic strategies for transplantation and various inflammatory cardiovascular, gastrointestinal and neurological diseases.

No MeSH data available.


Related in: MedlinePlus