Purinergic Signalling

, Volume 8, Issue 3, pp 437–502 | Cite as

Cellular function and molecular structure of ecto-nucleotidases

  • Herbert ZimmermannEmail author
  • Matthias Zebisch
  • Norbert Sträter
Original Article


Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ecto-nucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.


Alkaline phosphatase Catalytic mechanism 5′-Nucleotidase Ecto-nucleotidase NPP NTPDase Nucleoside triphosphate diphosphohydrolase Nucleotide pyrophosphatase/phosphodiesterase 



Apyrase-conserved regions




β,γ-Imidoadenosine 5′-triphosphate


Alkaline phosphatases




Calcium-activated nucleotidase


Chinese hamster ovary


Extracellular domain




Endoplasmic reticulum


Fluorescence resonance energy transfer


Germ cell AP






Intestinal AP


Lysophosphatidic acid






Matrix-assisted laser desorption/ionization


Madin–Darby canine kidney


Mass spectrometry


Nucleoside diphosphate


Nuclease-like domain


Nucleoside monophosphate


Nicotinamide mononucleotide


Nuclear magnetic resonance


Nucleotide pyrophosphatase/phosphodiesterase


Nicotinamide riboside


Nucleoside triphosphate


Nucleoside triphosphate diphosphohydrolase


Prostatic acid phosphatase


Protein Data Bank




Phosphatidylinositol-specific phospholipase C


Placental AP


Pyridoxal 5′-phosphate


Phorbol myristate acetate


p-Nitrophenyl phosphorylcholine






Somatomedin B




Ran Binding Protein M


Transmembrane domain


Tissue nonspecific AP


Tartrate-resistant acid phosphatase



The research work of the authors was supported by the Deutsche Forschungsgemeinschaft (to HZ: 140/17-4; Zi 140/18-1 and to NS: Str 477/11, Str 477/12, Str 477/13).


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Herbert Zimmermann
    • 1
    Email author
  • Matthias Zebisch
    • 2
  • Norbert Sträter
    • 3
  1. 1.Institute of Cell Biology and Neuroscience, Molecular and Cellular Neurobiology, BiologicumGoethe-University FrankfurtFrankfurt am MainGermany
  2. 2.Division of Structural Biology, Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
  3. 3.Center for Biotechnology and Biomedicine, Institute of Bioanalytical ChemistryUniversity of LeipzigLeipzigGermany

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