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Purinergic Signalling

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

Cellular function and molecular structure of ecto-nucleotidases

  • Herbert Zimmermann
  • Matthias Zebisch
  • Norbert Sträter
Original Article

Abstract

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.

Keywords

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

Abbreviations

ACR

Apyrase-conserved regions

AMPCP

α,β-Methylene-ADP

AMPPNP

β,γ-Imidoadenosine 5′-triphosphate

AP

Alkaline phosphatases

ATX

Autotaxin

CAN

Calcium-activated nucleotidase

CHO

Chinese hamster ovary

ECD

Extracellular domain

eN

5′-Nucleotidase

ER

Endoplasmic reticulum

FRET

Fluorescence resonance energy transfer

GCAP

Germ cell AP

GPC

Glycerophosphorylcholine

GPI

Glycosylphosphatidylinositol

IAP

Intestinal AP

LPA

Lysophosphatidic acid

LPC

Lysophosphatidylcholine

LPS

Lipopolysaccharide

MALDI

Matrix-assisted laser desorption/ionization

MDCK

Madin–Darby canine kidney

MS

Mass spectrometry

NDP

Nucleoside diphosphate

NLD

Nuclease-like domain

NMP

Nucleoside monophosphate

NMN

Nicotinamide mononucleotide

NMR

Nuclear magnetic resonance

NPP

Nucleotide pyrophosphatase/phosphodiesterase

NR

Nicotinamide riboside

NTP

Nucleoside triphosphate

NTPDase

Nucleoside triphosphate diphosphohydrolase

PAP

Prostatic acid phosphatase

PDB

Protein Data Bank

PDE

Phosphodiesterase

PI-PLC

Phosphatidylinositol-specific phospholipase C

PLAP

Placental AP

PLP

Pyridoxal 5′-phosphate

PMA

Phorbol myristate acetate

pNPPC

p-Nitrophenyl phosphorylcholine

PPi

Pyrophosphate

S1P

Sphingosine-1-phosphate

SMB

Somatomedin B

SPC

Sphingosylphosphorylcholine

RanBPM

Ran Binding Protein M

TMD

Transmembrane domain

TNAP

Tissue nonspecific AP

TRAP

Tartrate-resistant acid phosphatase

Notes

Acknowledgments

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
  • 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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