Structural highlights
Function
[NEUA_MOUSE] Catalyzes the activation of N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a substrate required for the addition of sialic acid. Has some activity toward NeuNAc, N-glycolylneuraminic acid (Neu5Gc) or 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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 A 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.
A C-terminal phosphatase module conserved in vertebrate CMP-sialic acid synthetases provides a tetramerization interface for the physiologically active enzyme.,Oschlies M, Dickmanns A, Haselhorst T, Schaper W, Stummeyer K, Tiralongo J, Weinhold B, Gerardy-Schahn R, von Itzstein M, Ficner R, Munster-Kuhnel AK J Mol Biol. 2009 Oct 16;393(1):83-97. Epub 2009 Aug 8. PMID:19666032[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Munster AK, Eckhardt M, Potvin B, Muhlenhoff M, Stanley P, Gerardy-Schahn R. Mammalian cytidine 5'-monophosphate N-acetylneuraminic acid synthetase: a nuclear protein with evolutionarily conserved structural motifs. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9140-5. PMID:9689047
- ↑ Oschlies M, Dickmanns A, Haselhorst T, Schaper W, Stummeyer K, Tiralongo J, Weinhold B, Gerardy-Schahn R, von Itzstein M, Ficner R, Munster-Kuhnel AK. A C-terminal phosphatase module conserved in vertebrate CMP-sialic acid synthetases provides a tetramerization interface for the physiologically active enzyme. J Mol Biol. 2009 Oct 16;393(1):83-97. Epub 2009 Aug 8. PMID:19666032 doi:10.1016/j.jmb.2009.08.003
