Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase
The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifical...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522002441 |
| _version_ | 1811172030500831232 |
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| author | Pengfei He Sha Wang Sen Li Siqi Liu Shuqi Zhou Jing Wang Jiayue Tao Dongdong Wang Rufeng Wang Wenfu Ma |
| author_facet | Pengfei He Sha Wang Sen Li Siqi Liu Shuqi Zhou Jing Wang Jiayue Tao Dongdong Wang Rufeng Wang Wenfu Ma |
| author_sort | Pengfei He |
| collection | DOAJ |
| description | The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry. |
| first_indexed | 2024-04-10T17:23:44Z |
| format | Article |
| id | doaj.art-6eb9a41145c649529e3ee7d76b526efc |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-10T17:23:44Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-6eb9a41145c649529e3ee7d76b526efc2023-02-05T04:15:57ZengElsevierActa Pharmaceutica Sinica B2211-38352023-01-01131246255Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerasePengfei He0Sha Wang1Sen Li2Siqi Liu3Shuqi Zhou4Jing Wang5Jiayue Tao6Dongdong Wang7Rufeng Wang8Wenfu Ma9School of Life Science, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Science, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Science, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Science, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Science, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Science, Beijing University of Chinese Medicine, Beijing 102488, ChinaSchool of Life Science, Beijing University of Chinese Medicine, Beijing 102488, ChinaDP Technology, Beijing 100080, ChinaSchool of Life Science, Beijing University of Chinese Medicine, Beijing 102488, China; Corresponding authors. Tel./fax: +86 10 53912152.School of Life Science, Beijing University of Chinese Medicine, Beijing 102488, China; Corresponding authors. Tel./fax: +86 10 53912152.The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.http://www.sciencedirect.com/science/article/pii/S2211383522002441C-GlycosideO-GlycosideC-Glycoside cleaving enzymeIsomeraseGut microbiotaFlavonoid |
| spellingShingle | Pengfei He Sha Wang Sen Li Siqi Liu Shuqi Zhou Jing Wang Jiayue Tao Dongdong Wang Rufeng Wang Wenfu Ma Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase Acta Pharmaceutica Sinica B C-Glycoside O-Glycoside C-Glycoside cleaving enzyme Isomerase Gut microbiota Flavonoid |
| title | Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase |
| title_full | Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase |
| title_fullStr | Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase |
| title_full_unstemmed | Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase |
| title_short | Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase |
| title_sort | structural mechanism of a dual functional enzyme dgpa b c as both a c glycoside cleaving enzyme and an o to c glycoside isomerase |
| topic | C-Glycoside O-Glycoside C-Glycoside cleaving enzyme Isomerase Gut microbiota Flavonoid |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522002441 |
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