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VOL. 73 (2), 537-566, 2007 ECTO-NUCLEOTIDASES, MOLECULAR PROPERTIES...

E-NTPDases

This enzyme family comprises eight different members of which
only NTPDase1-3 and 8 are typical cell surface-located enzymes, with
two transmembrane helices and a large extracellular domain carrying
the catalytic site (40, 41, 55) (Figure 2). Of the intracellular enzymes
(NTPDase4-7) that hydrolyze nucleoside diphosphates and/or
triphosphates but not ATP, NTPDase6 and NTPDas6 can be released
in soluble form. All enzymes are members of the actin/HSP70/sugar
kinase superfamily with whom they share common sequence motifs
as well as a conserved secondary structure (56, 57). Structural
predictions have been derived from mutagenic analyses and
computational modeling based on homology with a bacterial
exopolyphosphatase (58). The ectoenzymes form homooligomeric
complexes. All members of the NTPase gene family are also expressed
in Xenopus (59).

The surface-located NTPDases1-3 and 8 reveal a partially
overlapping tissue distribution but apparently are expressed by
different cells (55, 60). NTPDase1 corresponds to the lymphoid cell
activation antigen CD39. It is expressed by cells of the immune
system, the quiescent vascular endothelium and a variety of other
cells including the microglia of the brain (41, 61, 62). NTPDase2 is
associated amongst others with the adventitial surfaces of the
muscularized vessels, microvascular pericytes, portal fibroblasts from
the liver, within taste papillae, the inner ear, with immature and
nonmyelinating Schwann cells of the peripheral nervous system (63)
and neural progenitor cells of the adult rodent brain (41, 64, 65).
NTPDase3 is expressed in brain and in a variety of other tissues (56,
66, 67) whereas expression of NTPDase8 in the brain is very low or
absent (55).

Importantly, the hydrolysis rates for nucleoside diphosphates vary
considerably between the four enzymes (60, 68). NTPDase2 stands
out for its high preference for nucleotide triphosphates and thus is
also referred to as an ecto-ATPase. In addition the enzymes differ
regarding product formation. Whereas NTPDase1 hydrolyzes ATP
directly to AMP with the production of minor amounts of free ADP,
ADP accumulates extracellularly on ATP hydrolysis by NTPDase2.
NTPDase3 and NTPDase8 reveal intermediate patterns of product

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