6VUE
wild-type choline TMA lyase in complex with 1-methyl-1,2,3,6-tetrahydropyridin-3-ol
Summary for 6VUE
| Entry DOI | 10.2210/pdb6vue/pdb |
| Descriptor | Choline trimethylamine-lyase, SODIUM ION, (3S)-1-methyl-1,2,3,6-tetrahydropyridin-3-ol, ... (4 entities in total) |
| Functional Keywords | choline-tma lyase, microbiome choline cutc inhibitor, lyase, lyase-inhibitor complex, lyase/inhibitor |
| Biological source | Desulfovibrio alaskensis (strain G20) |
| Total number of polymer chains | 2 |
| Total formula weight | 183444.55 |
| Authors | Ortega, M.A.,Drennan, C.L. (deposition date: 2020-02-15, release date: 2020-11-04, Last modification date: 2023-10-11) |
| Primary citation | Bollenbach, M.,Ortega, M.,Orman, M.,Drennan, C.L.,Balskus, E.P. Discovery of a Cyclic Choline Analog That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria. Acs Med.Chem.Lett., 11:1980-1985, 2020 Cited by PubMed Abstract: The anaerobic conversion of choline to trimethylamine (TMA) by the human gut microbiota has been linked to multiple human diseases. The potential impact of this microbial metabolic activity on host health has inspired multiple efforts to identify small molecule inhibitors. Here, we use information about the structure and mechanism of the bacterial enzyme choline TMA-lyase (CutC) to develop a cyclic choline analog that inhibits the conversion of choline to TMA in bacterial whole cells and in a complex gut microbial community. biochemical assays and a crystal structure suggest that this analog is a competitive, mechanism-based inhibitor. This work demonstrates the utility of structure-based design to access inhibitors of radical enzymes from the human gut microbiota. PubMed: 33062182DOI: 10.1021/acsmedchemlett.0c00005 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.28 Å) |
Structure validation
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