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Escherichia coli FolC structure reveals an unexpected dihydrofolate binding site providing an attractive target for anti-microbial therapy.

Mathieu M, Debousker G, Vincent S, Viviani F, Bamas-Jacques N, Mikol V
J Biol Chem 280 18916-22 (2005)
Cited: 25 times
EuropePMC logo PMID: 15705579

Abstract

In some bacteria, such as Escherichia coli, the addition of L-glutamate to dihydropteroate (dihydrofolate synthetase activity) and the subsequent additions of L-glutamate to tetrahydrofolate (folylpolyglutamate synthetase (FPGS) activity) are catalyzed by the same enzyme, FolC. The crystal structure of E. coli FolC is described in this paper. It showed strong similarities to that of the FPGS enzyme of Lactobacillus casei within the ATP binding site and the catalytic site, as do all other members of the Mur synthethase superfamily. FolC structure revealed an unexpected dihydropteroate binding site very different from the folate site identified previously in the FPGS structure. The relevance of this site is exemplified by the presence of phosphorylated dihydropteroate, a reaction intermediate in the DHFS reaction. L. casei FPGS is considered a relevant model for human FPGS. As such, the presence of a folate binding site in E. coli FolC, which is different from the one seen in FPGS enzymes, provides avenues for the design of specific inhibitors of this enzyme in antimicrobial therapy.

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  14. The uridylyltransferase GlnD and tRNA modification GTPase MnmE allosterically control Escherichia coli folylpoly-γ-glutamate synthase FolC. Rodionova IA, Goodacre N, Do J, Hosseinnia A, Babu M, Uetz P, Saier MH. J Biol Chem 293 15725-15732 (2018)
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  17. Purification, crystallization and preliminary X-ray analysis of Mycobacterium tuberculosisfolylpolyglutamate synthase (MtbFPGS). Young PG, Smith CA, Sun X, Baker EN, Metcalf P. Acta Crystallogr Sect F Struct Biol Cryst Commun 62 579-582 (2006)
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