論文 - 詳細
| RRC ID | 75234 |
|---|---|
| 著者 | Makino Y, Oe C, Iwama K, Suzuki S, Nishiyama A, Hasegawa K, Okuda H, Hirata K, Ueno M, Kawaji K, Sasano M, Usui E, Hosaka T, Yabuki Y, Shirouzu M, Katsumi M, Murayama K, Hayashi H, Kodama EN. |
| タイトル | Serine hydroxymethyltransferase as a potential target of antibacterial agents acting synergistically with one-carbon metabolism-related inhibitors. |
| ジャーナル | Commun Biol |
| Abstract |
Serine hydroxymethyltransferase (SHMT) produces 5,10-methylenetetrahydrofolate (CH2-THF) from tetrahydrofolate with serine to glycine conversion. SHMT is a potential drug target in parasites, viruses and cancer. (+)-SHIN-1 was developed as a human SHMT inhibitor for cancer therapy. However, the potential of SHMT as an antibacterial target is unknown. Here, we show that (+)-SHIN-1 bacteriostatically inhibits the growth of Enterococcus faecium at a 50% effective concentration of 10-11 M and synergistically enhances the antibacterial activities of several nucleoside analogues. Our results, including crystal structure analysis, indicate that (+)-SHIN-1 binds tightly to E. faecium SHMT (efmSHMT). Two variable loops in SHMT are crucial for inhibitor binding, and serine binding to efmSHMT enhances the affinity of (+)-SHIN-1 by stabilising the loop structure of efmSHMT. The findings highlight the potency of SHMT as an antibacterial target and the possibility of developing SHMT inhibitors for treating bacterial, viral and parasitic infections and cancer. |
| 巻・号 | 5(1) |
| ページ | 619 |
| 公開日 | 2022-6-23 |
| DOI | 10.1038/s42003-022-03555-x |
| PII | 10.1038/s42003-022-03555-x |
| PMID | 35739195 |
| PMC | PMC9223267 |
| MeSH | Anti-Bacterial Agents / pharmacology Carbon Glycine Hydroxymethyltransferase* / chemistry Glycine Hydroxymethyltransferase* / metabolism Humans Neoplasms* Serine / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 一般微生物 | JCM 5804 JCM 7783 |