1fgs
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FOLYLPOLYGLUTAMATE SYNTHETASE FROM LACTOBACILLUS CASEI
OverviewOverview
Folylpolyglutamate synthetase, which is responsible for the addition of a, polyglutamate tail to folate and folate derivatives, is an ATP-dependent, enzyme isolated from eukaryotic and bacterial sources, where it plays a, key role in the retention of the intracellular folate pool. Here, we, report the 2.4-A resolution crystal structure of the MgATP complex of the, enzyme from Lactobacillus casei. The structural analysis reveals that, folylpolyglutamate synthetase is a modular protein consisting of two, domains, one with a typical mononucleotide-binding fold and the other, strikingly similar to the folate-binding enzyme dihydrofolate reductase., We have located the active site of the enzyme in a large interdomain cleft, adjacent to an ATP-binding P-loop motif. Opposite this site, in the C, domain, a cavity likely to be the folate binding site has been identified, and inspection of this cavity and the surrounding protein structure, suggests that the glutamate tail of the substrate may project into the, active site. A further feature of the structure is a well defined Omega, loop, which contributes both to the active site and to interdomain, interactions. The determination of the structure of this enzyme represents, the first step toward the elucidation of the molecular mechanism of, polyglutamylation of folates and antifolates.
About this StructureAbout this Structure
1FGS is a Single protein structure of sequence from Lactobacillus casei with MG and POP as ligands. Active as Tetrahydrofolate synthase, with EC number 6.3.2.17 Full crystallographic information is available from OCA.
ReferenceReference
Structural homologies with ATP- and folate-binding enzymes in the crystal structure of folylpolyglutamate synthetase., Sun X, Bognar AL, Baker EN, Smith CA, Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6647-52. PMID:9618466
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