6W0S
Crystal structure of substrate free cytochrome P450 NasF5053 from Streptomyces sp. NRRL F-5053
Summary for 6W0S
| Entry DOI | 10.2210/pdb6w0s/pdb |
| Descriptor | cytochrome P450-F5053, GLYCEROL, BROMIDE ION, ... (7 entities in total) |
| Functional Keywords | biosynthetic protein, cytochrome p450, cyclodipeptide, regio-selecitivty, stereo-selectivity, pyrroloindoline alkaloids, radical mediated reaction, f5053, streptomyces, oxidoreductase |
| Biological source | Streptomyces sp. NRRL F-5053 |
| Total number of polymer chains | 2 |
| Total formula weight | 88821.53 |
| Authors | |
| Primary citation | Sun, C.,Luo, Z.,Zhang, W.,Tian, W.,Peng, H.,Lin, Z.,Deng, Z.,Kobe, B.,Jia, X.,Qu, X. Molecular basis of regio- and stereo-specificity in biosynthesis of bacterial heterodimeric diketopiperazines. Nat Commun, 11:6251-6251, 2020 Cited by PubMed Abstract: Bacterial heterodimeric tryptophan-containing diketopiperazines (HTDKPs) are a growing family of bioactive natural products. They are challenging to prepare by chemical routes due to the polycyclic and densely functionalized backbone. Through functional characterization and investigation, we herein identify a family of three related HTDKP-forming cytochrome P450s (NasbB, Nas and Nas) and reveal four critical residues (Qln65, Ala86, Ser284 and Val288) that control their regio- and stereo-selectivity to generate diverse dimeric DKP frameworks. Engineering these residues can alter the specificities of the enzymes to produce diverse frameworks. Determining the crystal structures (1.70-1.47 Å) of Nas (ligand-free and substrate-bound Nas and its Q65I-A86G and S284A-V288A mutants) and molecular dynamics simulation finally elucidate the specificity-conferring mechanism of these residues. Our results provide a clear molecular and mechanistic basis into this family of HTDKP-forming P450s, laying a solid foundation for rapid access to the molecular diversity of HTDKP frameworks through rational engineering of the P450s. PubMed: 33288748DOI: 10.1038/s41467-020-20022-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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