Structural Analyses of Helicobacter Pylori FolC Conducting Glutamation in Folate Metabolism
- Authors
- Park, Joon Sung; Kim, Hyoun Sook; Park, Sang Ho; Park, Mi Seul; Kang, Sung-Min; Kim, Hyun-Jung; Han, Byung Woo
- Issue Date
- Aug-2019
- Publisher
- MDPI
- Keywords
- bifunctional FolC; dihydrofolate synthetase (DHFS); folate metabolism; folylpolyglutamate synthetase (FPGS); Helicobacter pylori
- Citation
- CRYSTALS, v.9, no.8
- Journal Title
- CRYSTALS
- Volume
- 9
- Number
- 8
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/44727
- DOI
- 10.3390/cryst9080429
- ISSN
- 2073-4352
- Abstract
- 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 angstrom 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 omega-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 omega-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.
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