|Gene:||NANS||Accession Number: G-11082 (MetaCyc)|
Species: Homo sapiens
This enzyme catalyzes a critical reaction in sialic acid biosynthesis, the condensation of phosphoenolpyruvate with N-acetyl-D-mannosamine 6-phosphate. Unlike the bacterial enzyme that uses N-acetyl-β-D-mannosamine as substrate, the animal enzyme uses the 6-phosphorylated derivative to produce N-acetyl-β-neuraminate 9-phosphate (see pathways CMP-N-acetylneuraminate biosynthesis I (eukaryotes) and CMP-N-acetylneuraminate biosynthesis II (bacteria)).
A key difference also exists in the human (this enzyme) versus rat N-acetylneuraminate 9-phosphate synthase and mouse N-acetylneuraminate 9-phosphate synthase enzymes. The human enzyme can also utilize α-D-mannose 6-phosphate to produce 2-keto-3-deoxy-D-glycero-D-galacto-nononate 9-phosphate in this reaction (see pathway CMP-2-keto-3-deoxy-D-glycero-D-galacto-nononate biosynthesis), whereas the rodent enzymes cannot (reviewed in [Tanner05]). Mutagenesis studies of the recombinant human enzyme revealed that a single mutation resulting in substitution of Thr for Met at position 42 eliminated the 2-keto-3-deoxy-D-glycero-D-galacto-nononate 9-phosphate synthase activity without affecting N-acetyl-β-neuraminate 9-phosphate synthase activity [Hao06].
Gene Citations: [Lawrence00]
|Map Position: [99,858,842 -> 99,885,178]|
Molecular Weight of Polypeptide: 40.308 kD (from nucleotide sequence)
Unification Links: ArrayExpress:Q9NR45 , Entrez-gene:54187 , Mint:MINT-5002014 , PhosphoSite:Q9NR45 , Pride:Q9NR45 , Protein Model Portal:Q9NR45 , SMR:Q9NR45 , String:9606.ENSP00000210444 , UniProt:Q9NR45
Relationship Links: InterPro:IN-FAMILY:IPR006013 , InterPro:IN-FAMILY:IPR006190 , InterPro:IN-FAMILY:IPR013132 , InterPro:IN-FAMILY:IPR013785 , InterPro:IN-FAMILY:IPR013974 , PDB:Structure:1WVO , Pfam:IN-FAMILY:PF03102 , Pfam:IN-FAMILY:PF08666 , Prints:IN-FAMILY:PR00357 , Prosite:IN-FAMILY:PS50844 , Smart:IN-FAMILY:SM00858
Enzymatic reaction of: N-acetylneuraminate 9-phosphate synthase (sialic acid synthase)
Synonyms: N-acetylneuraminate phosphate synthase, N-acetylneuraminic acid phosphate synthase, N-acetylneuraminic acid 9-phosphate synthase, sialic acid (N-acetylneuraminic acid) synthase, sialic acid synthase
EC Number: 188.8.131.52
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
The reaction is favored in the direction shown.
Recombinant human enzyme containing a hexahistidine tag and Myc peptide epitope was expressed in Escherichia coli, purified and assayed for activity. Recombinant enzyme was also expressed in Sf9 insect cells and activity was assayed in cell lysates. Additionally, recombinant human enzyme was shown to complement a sialic acid synthase negative Escherichia coli K1 mutant [Lawrence00].
The recombinant human enzyme expressed in insect cells was shown to use either N-acetyl-D-mannosamine 6-phosphate to produce N-acetyl-β-neuraminate 9-phosphate, or α-D-mannose 6-phosphate to produce 2-keto-3-deoxy-D-glycero-D-galacto-nononate. However it showed higher activity toward formatin of N-acetyl-β-neuraminate 9-phosphate [Lawrence00].
The mechanism of this condensation reaction remains to be completely elucidated, although possible mechanisms have been considered that involve either C-O, or P-O bond cleavage (reviewed in [Tanner05]).
Chen02a: Chen H, Blume A, Zimmermann-Kordmann M, Reutter W, Hinderlich S (2002). "Purification and characterization of N-acetylneuraminic acid-9-phosphate synthase from rat liver." Glycobiology 12(2);65-71. PMID: 11886839
Hao06: Hao J, Vann WF, Hinderlich S, Sundaramoorthy M (2006). "Elimination of 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid 9-phosphate synthase activity from human N-acetylneuraminic acid 9-phosphate synthase by a single mutation." Biochem J 397(1);195-201. PMID: 16503877
Lawrence00: Lawrence SM, Huddleston KA, Pitts LR, Nguyen N, Lee YC, Vann WF, Coleman TA, Betenbaugh MJ (2000). "Cloning and expression of the human N-acetylneuraminic acid phosphate synthase gene with 2-keto-3-deoxy-D-glycero- D-galacto-nononic acid biosynthetic ability." J Biol Chem 275(23);17869-77. PMID: 10749855
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