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Open AccessArticle

Structural Analyses of Helicobacter Pylori FolC Conducting Glutamation in Folate Metabolism

1
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
2
Division of Precision Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Korea
3
College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Korea
*
Author to whom correspondence should be addressed.
Crystals 2019, 9(8), 429; https://doi.org/10.3390/cryst9080429
Received: 26 July 2019 / Revised: 15 August 2019 / Accepted: 17 August 2019 / Published: 19 August 2019
(This article belongs to the Special Issue Crystallographic Studies of Enzymes)
FolC plays important roles in the folate metabolism of cells by attaching l-Glu to dihydropteroate (DHP) and folate, which are known activities of dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS), respectively. Here, we determined the crystal structure of Helicobacter pylori FolC (HpFolC) at 1.95 Å resolution using the single-wavelength anomalous diffraction method. HpFolC has globular N- and C-terminal domains connected by a single loop, and a binding site for ATP is located between the two domains. Apo-HpFolC was crystallized in the presence of citrate in a crystallization solution, which was held in the ATP-binding site. Structural motifs such as the P-loop and Ω-loop of HpFolC for binding of ATP and two magnesium ions are well conserved in spite of the low overall sequence similarity to other FolC/FPGSs. The Ω-loop would also recognize a folate molecule, and the DHP-binding loop of HpFolC is expected to exhibit a unique recognition mode on DHP, compared with other FolCs. Because human FolC is known to only exhibit FPGS activity, the DHFS activity of bacterial FolC is an attractive target for the eradication of pathogenic bacteria. Consequently, our structural analyses of HpFolC provide a valuable foundation for a universal antibacterial strategy against H. pylori as well as other pathogenic bacteria. View Full-Text
Keywords: bifunctional FolC; dihydrofolate synthetase (DHFS); folate metabolism; folylpolyglutamate synthetase (FPGS); Helicobacter pylori bifunctional FolC; dihydrofolate synthetase (DHFS); folate metabolism; folylpolyglutamate synthetase (FPGS); Helicobacter pylori
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Park, J.S.; Kim, H.S.; Park, S.H.; Park, M.S.; Kang, S.-M.; Kim, H.-J.; Han, B.W. Structural Analyses of Helicobacter Pylori FolC Conducting Glutamation in Folate Metabolism. Crystals 2019, 9, 429.

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