A C-terminal phosphatase module conserved in vertebrate CMP-sialic acid synthetases provides a tetramerization interface for the physiologically active enzyme

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Title A C-terminal phosphatase module conserved in vertebrate CMP-sialic acid synthetases provides a tetramerization interface for the physiologically active enzyme
Author Oschlies, Melanie; Dickmanns, Achim; Haselhorst, Thomas Erwin; Schaper, Wiebke; Stummeyer, Katharina; Tiralongo, Giuseppe; Weinhold, Birgit; Gerardy-Schahn, Rita; von Itzstein, Mark; Ficner, Ralf; Munster-Kuhnel, Anja-K.
Journal Name Journal of Molecular Biology
Year Published 2009
Place of publication United Kingdom
Publisher Elsevier
Abstract The biosynthesis of sialic acid-containing glycoconjugates is crucial for the development of vertebrate life. Cytidine monophosphate-sialic acid synthetase (CSS) catalyzes the metabolic activation of sialic acids. In vertebrates, the enzyme is chimeric, with the N-terminal domain harboring the synthetase activity. The function of the highly conserved C-terminal domain (CSS-CT) is unknown. To shed light on its biological function, we solved the X-ray structure of murine CSS-CT to 1.9 Å resolution. CSS-CT is a stable shamrock-like tetramer that superimposes well with phosphatases of the haloacid dehalogenase superfamily. However, a region found exclusively in vertebrate CSS-CT appears to block the active-site entrance. Accordingly, no phosphatase activity was observed in vitro, which points toward a nonenzymatic function of CSS-CT. A computational three-dimensional model of full-length CSS, in combination with in vitro oligomerization studies, provides evidence that CSS-CT serves as a platform for the quaternary organization governing the kinetic properties of the physiologically active enzyme as demonstrated in kinetic studies.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.jmb.2009.08.003
Volume 393
Issue Number 1
Page from 83
Page to 97
ISSN 0022-2836
Date Accessioned 2010-02-18
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Characterisation of Biological Macromolecules
URI http://hdl.handle.net/10072/30542
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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