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
Sialic acids are activated by CMP-5-N-acetylneuraminic acid synthetase prior to their transfer onto oligo- or polysaccharides. Here, we present the crystal structure of the N-terminal catalytically active domain of the murine 5-N-acetylneuraminic acid synthetase in complex with the reaction product. In contrast to the previously solved structure of 5-N-acetylneuraminic acid synthetase from Neisseria meningitidis and the related CMP-KDO-synthetase of Escherichia coli, the murine enzyme is a tetramer, which was observed with the active sites closed. In this conformation a loop is shifted by 6A towards the active site and thus an essential arginine residue can participate in catalysis. Furthermore, a network of intermolecular salt-bridges and hydrogen bonds in the dimer as well as hydrophobic interfaces between two dimers indicate a cooperative behaviour of the enzyme. In addition, a complex regulation of the enzyme activity is proposed that includes phosphorylation and dephosphorylation.
The crystal structure of murine CMP-5-N-acetylneuraminic acid synthetase.,Krapp S, Munster-Kuhnel AK, Kaiser JT, Huber R, Tiralongo J, Gerardy-Schahn R, Jacob U J Mol Biol. 2003 Dec 5;334(4):625-37. PMID:14636592[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
- ↑ Krapp S, Munster-Kuhnel AK, Kaiser JT, Huber R, Tiralongo J, Gerardy-Schahn R, Jacob U. The crystal structure of murine CMP-5-N-acetylneuraminic acid synthetase. J Mol Biol. 2003 Dec 5;334(4):625-37. PMID:14636592
