8HO0
Crystal structure of cytochrome P450 NasF5053 mutant E73S complexed with 8FCWP
Summary for 8HO0
Entry DOI | 10.2210/pdb8ho0/pdb |
Descriptor | Cytochrome P450-F5053, PROTOPORPHYRIN IX CONTAINING FE, (3~{S},8~{a}~{S})-3-[(7-fluoranyl-1~{H}-indol-3-yl)methyl]-2,3,6,7,8,8~{a}-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione, ... (5 entities in total) |
Functional Keywords | p450, oxidoreductase |
Biological source | Streptomyces sp. NRRL F-5053 |
Total number of polymer chains | 1 |
Total formula weight | 44374.92 |
Authors | Ma, B.D.,Tian, W.,Qu, X.,Kong, X.D. (deposition date: 2022-12-09, release date: 2023-04-19, Last modification date: 2024-05-29) |
Primary citation | Sun, C.,Ma, B.D.,Li, G.,Tian, W.,Yang, L.,Peng, H.,Lin, Z.,Deng, Z.,Kong, X.D.,Qu, X. Engineering the Substrate Specificity of a P450 Dimerase Enables the Collective Biosynthesis of Heterodimeric Tryptophan-Containing Diketopiperazines. Angew.Chem.Int.Ed.Engl., 62:e202304994-e202304994, 2023 Cited by PubMed Abstract: Heterodimeric tryptophan-containing diketopiperazines (HTDKPs) are an important class of bioactive secondary metabolites. Biosynthesis offers a practical opportunity to access their bioactive structural diversity, however, it is restricted by the limited substrate scopes of the HTDKPs-forming P450 dimerases. Herein, by genome mining and investigation of the sequence-product relationships, we unveiled three important residues (F387, F388 and E73) in these P450s that are pivotal for selecting different diketopiperazine (DKP) substrates in the upper binding pocket. Engineering these residues in Nas significantly expanded its substrate specificity and enabled the collective biosynthesis, including 12 self-dimerized and at least 81 cross-dimerized HTDKPs. Structural and molecular dynamics analysis of F387G and E73S revealed that they control the substrate specificity via reducing steric hindrance and regulating substrate tunnels, respectively. PubMed: 37083030DOI: 10.1002/anie.202304994 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.71 Å) |
Structure validation
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