5VWS
Ligand free structure of Cytochrome P450 TbtJ1
Summary for 5VWS
| Entry DOI | 10.2210/pdb5vws/pdb |
| Descriptor | Cytochrome P450, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total) |
| Functional Keywords | cytochrome p450, thiomuracin gz, oxidoreductase |
| Biological source | Thermobispora bispora (strain ATCC 19993 / DSM 43833 / CBS 139.67 / JCM 10125 / NBRC 14880 / R51) |
| Total number of polymer chains | 1 |
| Total formula weight | 45274.38 |
| Authors | Gober, J.G.,Ghodge, S.V.,Brustad, E.M.,Bowers, A.A. (deposition date: 2017-05-22, release date: 2017-06-07, Last modification date: 2023-10-04) |
| Primary citation | Gober, J.G.,Ghodge, S.V.,Bogart, J.W.,Wever, W.J.,Watkins, R.R.,Brustad, E.M.,Bowers, A.A. P450-Mediated Non-natural Cyclopropanation of Dehydroalanine-Containing Thiopeptides. ACS Chem. Biol., 12:1726-1731, 2017 Cited by PubMed Abstract: Thiopeptides are a growing class of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products. Many biosynthetic enzymes for RiPPs, especially thiopeptides, are promiscuous and can accept a wide range of peptide substrates with different amino acid sequences; thus, these enzymes have been used as tools to generate new natural product derivatives. Here, we explore an alternative route to molecular complexity by engineering thiopeptide tailoring enzymes to do new or non-native chemistry. We explore cytochrome P450 enzymes as biocatalysts for cyclopropanation of dehydroalanines, chemical motifs found widely in thiopeptides and other RiPP-based natural products. We find that P450 and P450 selectively cyclopropanate dehydroalanines in a number of complex thiopeptide-based substrates and convert them into 1-amino-2-cyclopropane carboxylic acids (ACCAs), which are important pharmacophores. This chemistry takes advantage of the innate affinity of these biosynthetic enzymes for their substrates and enables incorporation of new pharmacophores into thiopeptide architectures. This work also presents a strategy for diversification of natural products through rationally repurposing biosynthetic enzymes as non-natural biocatalysts. PubMed: 28535034DOI: 10.1021/acschembio.7b00358 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.411 Å) |
Structure validation
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