Tetrahydrofolate synthase

In enzymology, a tetrahydrofolate synthase (EC 6.3.2.17) is an enzyme that catalyzes the chemical reaction

ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate ${\displaystyle \rightleftharpoons }$ ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n⁺1

The 3 substrates of this enzyme are ATP, [[tetrahydropteroyl-[gamma-Glu]n]], and L-glutamate, whereas its 3 products are ADP, phosphate, and [[tetrahydropteroyl-[gamma-Glu]n+1]].

This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds as acid-D-amino-acid ligases (peptide synthases). The systematic name of this enzyme class is tetrahydropteroyl-gamma-polyglutamate:L-glutamate gamma-ligase (ADP-forming). This enzyme participates in folate biosynthesis.

As of late 2007, 7 structures have been solved for this class of enzymes, with PDB accession codes 1FGS, 1JBV, 1JBW, 2GC5, 2GC6, 2GCA, and 2GCB.

• Cichowicz DJ, Foo SK, Shane B (1981). "Folylpoly-gamma-glutamate synthesis by bacteria and mammalian cells". Mol. Cell. Biochem. 39: 209–28. doi:10.1007/BF00232575. PMID 6458762. S2CID 43985411.
• McGuire JJ, Bertino JR (1981). "Enzymatic synthesis and function of folylpolyglutamates". Mol. Cell. Biochem. 38 (Pt 1): 19–48. doi:10.1007/BF00235686. PMID 7027025. S2CID 9149947.
• Bognar AL, Osborne C, Shane B, Singer SC, Ferone R (1985). "Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase Cloning and high expression of the Escherichia coli folC gene and purification and properties of the gene product". J. Biol. Chem. 260 (9): 5625–30. doi:10.1016/S0021-9258(18)89069-X. PMID 2985605.
• R Rebeille F; Cherest, H; Jabrin, S; Grunwald, D; Surdin-Kerjan, Y; Douce, R; Rébeillé, F (2001). "Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana". Proc. Natl. Acad. Sci. U.S.A. 98 (26): 15360–5. Bibcode:2001PNAS...9815360R. doi:10.1073/pnas.261585098. PMC 65034. PMID 11752472.
• Cossins EA, Chen L (1997). "Folates and one-carbon metabolism in plants and fungi". Phytochemistry. 45 (3): 437–52. Bibcode:1997PChem..45..437C. doi:10.1016/S0031-9422(96)00833-3. PMID 9190084.
• Cherest H, Thomas D, Surdin-Kerjan Y (2000). "Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae". J. Biol. Chem. 275 (19): 14056–63. doi:10.1074/jbc.275.19.14056. PMID 10799479.

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