3EWI

Structural analysis of the C-terminal domain of murine CMP-Sialic acid Synthetase

Summary for 3EWI

• Entry DOI: 10.2210/pdb3ewi/pdb
• Related: 1QWJ
• Descriptor: N-acylneuraminate cytidylyltransferase (2 entities in total)
• Functional Keywords: beta barrel, had-like, rossmannoid fold, nucleotidyltransferase, nucleus, transferase
• Biological source: Mus Musculus (mouse)
• Cellular location: Nucleus : Q99KK2
• Total number of polymer chains: 2
• Total formula weight: 36744.59

Authors

Oschlies, M.,Dickmanns, A.,Stummeyer, K.,Gerardy-Schahn, R.,Ficner, R.,Muenster-Kuehnel, A.K. (deposition date: 2008-10-15, release date: 2009-08-18, Last modification date: 2023-12-27)

Primary citation

Oschlies, M.,Dickmanns, A.,Haselhorst, T.,Schaper, W.,Stummeyer, K.,Tiralongo, J.,Weinhold, B.,Gerardy-Schahn, R.,von Itzstein, M.,Ficner, R.,Munster-Kuhnel, A.K.
A C-terminal phosphatase module conserved in vertebrate CMP-sialic acid synthetases provides a tetramerization interface for the physiologically active enzyme.
J.Mol.Biol., 393:83-97, 2009

PubMed 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 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.

PubMed: 19666032
DOI: 10.1016/j.jmb.2009.08.003

Experimental method

X-RAY DIFFRACTION (1.9 Å)