In enzymology, a lactosylceramide alpha-2,3-sialyltransferase (EC 2.4.99.9) is an enzyme that catalyzes the chemical reaction
CMP-N-acetylneuraminate + beta-D-galactosyl-1,4-beta-D-glucosylceramide ⇌ {\displaystyle \rightleftharpoons } CMP + alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D- glucosylceramide Thus, the two substrates of this enzyme are CMP-N-acetylneuraminate and beta-D-galactosyl-1,4-beta-D-glucosylceramide, whereas its 3 products are CMP, alpha-N-acetylneuraminyl-2,3-beta-D-galactosyl-1,4-beta-D-, and glucosylceramide. This enzyme belongs to the family of transferases, specifically those glycosyltransferases that do not transfer hexosyl or pentosyl groups. The systematic name of this enzyme class is CMP-N-acetylneuraminate:lactosylceramide alpha-2,3-N-acetylneuraminyltransferase. Other names in common use include cytidine monophosphoacetylneuraminate-lactosylceramide alpha2,3-, sialyltransferase, CMP-acetylneuraminate-lactosylceramide-sialyltransferase, CMP-acetylneuraminic acid:lactosylceramide sialyltransferase, CMP-sialic acid:lactosylceramide-sialyltransferase, cytidine monophosphoacetylneuraminate-lactosylceramide, sialyltransferase, ganglioside GM3 synthetase, GM3 synthase, GM3 synthetase, and SAT 1. This enzyme participates in glycosphingolipid biosynthesis - ganglioseries and glycan structures - biosynthesis 2.
Structural studies As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes PDB: 2EX0 and PDB: 2EX1.
Function Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The enzyme is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene.
Gene
Lactosylceramide alpha-2,3-sialyltransferase is encoded in humans by the ST3GAL5 gene. Mutations in this gene have also been associated to ‘Salt & Pepper’ syndrome: an autosomal recessive condition characterized by severe intellectual disability, epilepsy, scoliosis, choreoathetosis, dysmorphic facial features and altered dermal pigmentation. (doi: 10.1093/hmg/ddt434)
References
Bibliography Basu S, Kaufman B, Roseman S (1973). "Enzymatic synthesis of glucocerebroside by a glucosyltransferase from embryonic chicken brain". J. Biol. Chem. 248 (4): 1388–94. doi:10.1016/S0021-9258(19)44311-1. PMID 4631392. Fishman PH, Bradley RM, Henneberry RC (1976). "Butyrate-induced glycolipid biosynthesis in HeLa cells: properties of the induced sialyltransferase". Arch. Biochem. Biophys. 172 (2): 618–26. doi:10.1016/0003-9861(76)90116-8. PMID 4022. Higashi H, Basu M, Basu S (1985). "Biosynthesis in vitro of disialosylneolactotetraosylceramide by a solubilized sialyltransferase from embryonic chicken brain". J. Biol. Chem. 260 (2): 824–8. doi:10.1016/S0021-9258(20)71172-5. PMID 3838172.
Further reading
