Voltage sensitive phosphatases: emerging kinship to
protein tyrosine phosphatases from structure-function
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Kirstin and Friedrich, Thomas
||Max-Volmer-Laboratory of Biophysical Chemistry, Institute of
Chemistry, Technische Universität Berlin Berlin, Germany.
transmembrane protein Ci-VSP from the ascidian Ciona intestinalis was
described as first member of a fascinating family of enzymes, the
voltage sensitive phosphatases (VSPs). Ci-VSP and its
voltage-activated homologs from other species are stimulated by
positive membrane potentials and dephosphorylate the head groups of
negatively charged phosphoinositide phosphates (PIPs). In doing so,
VSPs act as control centers at the cytosolic membrane surface, because
they intervene in signaling cascades that are mediated by PIP lipids.
The characteristic motif CX5RT/S in the active site classifies VSPs as
members of the huge family of cysteine-based protein tyrosine
phosphatases (PTPs). Although PTPs have already been
well-characterized regarding both, structure and function, their
relationship to VSPs has drawn only limited attention so far.
Therefore, the intention of this review is to give a short overview
about the extensive knowledge about PTPs in relation to the facts
known about VSPs. Here, we concentrate on the structural features of
the catalytic domain which are similar between both classes of
phosphatases and their consequences for the enzymatic function. By
discussing results obtained from crystal structures, molecular
dynamics simulations, and mutagenesis studies, a possible mechanism
for the catalytic cycle of VSPs is presented based on that one
proposed for PTPs. In this way, we want to link the knowledge about
the catalytic activity of VSPs and PTPs.
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