6KFW
The cytochrome P450 enzyme CxnD for C-S bond formation in chuangxinmycin biosynthesis
Summary for 6KFW
| Entry DOI | 10.2210/pdb6kfw/pdb |
| Descriptor | CxnD, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | p450, cxnd, oxidoreductase |
| Biological source | Actinoplanes tsinanensis |
| Total number of polymer chains | 1 |
| Total formula weight | 46512.51 |
| Authors | Hong, B. (deposition date: 2019-07-09, release date: 2020-07-15, Last modification date: 2023-11-22) |
| Primary citation | Shi, Y.,Jiang, Z.,Hu, X.,Hu, X.,Gu, R.,Jiang, B.,Zuo, L.,Li, X.,Sun, H.,Zhang, C.,Wang, L.,Wu, L.,Hong, B. The Cytochrome P450 Catalyzing C-S Bond Formation in S-Heterocyclization of Chuangxinmycin Biosynthesis. Angew.Chem.Int.Ed.Engl., 60:15399-15404, 2021 Cited by PubMed Abstract: Microbial sulfur-containing secondary metabolites show various biological activities, but the C-S bond-forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C-S bond forming activity in S-heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a L-Trp-derived thiol intermediate. Furthermore, X-ray crystal structure of CxnD in complex with a substrate analogue and structure-based mutagenesis revealed intimate details of the substrate binding mode. A radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD, which provided valuable insights into the molecular basis for the intra-molecular C(sp )-H thiolation by the P450 in chuangxinmycin biosynthesis. PubMed: 33884733DOI: 10.1002/anie.202015814 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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