8TWU
Crystal structure of Cytochrome P450 AspB bound to N1-methylated cyclo-L-Trp-L-Pro
Summary for 8TWU
| Entry DOI | 10.2210/pdb8twu/pdb |
| Descriptor | Cytochrome P450 AspB, PROTOPORPHYRIN IX CONTAINING FE, (3S,5S,8aS)-3-[(1-methyl-1H-indol-3-yl)methyl]hexahydropyrrolo[1,2-a]pyrazine-1,4-dione, ... (5 entities in total) |
| Functional Keywords | dimerase, oxidoreductase |
| Biological source | Streptomyces |
| Total number of polymer chains | 1 |
| Total formula weight | 45835.94 |
| Authors | Gering, H.E.,Li, X.,Tang, H.,Swartz, P.D.,Chang, W.-C.,Makris, T.M. (deposition date: 2023-08-21, release date: 2023-09-20) |
| Primary citation | Gering, H.E.,Li, X.,Tang, H.,Swartz, P.D.,Chang, W.C.,Makris, T.M. A Ferric-Superoxide Intermediate Initiates P450-Catalyzed Cyclic Dipeptide Dimerization. J.Am.Chem.Soc., 145:19256-19264, 2023 Cited by PubMed Abstract: The cytochrome P450 (CYP) AspB is involved in the biosynthesis of the diketopiperazine (DKP) aspergilazine A. Tryptophan-linked dimeric DKP alkaloids are a large family of natural products that are found in numerous species and exhibit broad and often potent bioactivity. The proposed mechanisms for C-N bond formation by AspB, and similar C-C bond formations by related CYPs, have invoked the use of a ferryl-intermediate as an oxidant to promote substrate dimerization. Here, the parallel application of steady-state and transient kinetic approaches reveals a very different mechanism that involves a ferric-superoxide species as a primary oxidant to initiate DKP-assembly. Single turnover kinetic isotope effects and a substrate analog suggest the probable nature and site for abstraction. The direct observation of CYP-superoxide reactivity rationalizes the atypical outcome of AspB and reveals a new reaction manifold in heme enzymes. PubMed: 37611404DOI: 10.1021/jacs.3c04542 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.84 Å) |
Structure validation
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