6M9R
Crystal structure of SznF from Streptomyces achromogenes var. streptozoticus NRRL 2697 with a bound N(delta)-hydroxy-N(omega)-methyl-L-arginine intermediate
Summary for 6M9R
| Entry DOI | 10.2210/pdb6m9r/pdb |
| Related | 6M9S |
| Descriptor | SznF, (2S)-2-amino-5-{[(E)-amino(methylamino)methylidene](hydroxy)azaniumyl}pentanoate, FE (III) ION, ... (4 entities in total) |
| Functional Keywords | non-heme iron-dependent, cupin domain, helix bundle, monooxygenase, n-nitrosation, l-arginine derivative, metal-bound, ligand-bound, anaerobic, oxidoreductase |
| Biological source | Streptomyces achromogenes subsp. streptozoticus |
| Total number of polymer chains | 2 |
| Total formula weight | 108262.51 |
| Authors | Rohac, R.,Mitchell, A.J.,Boal, A.K. (deposition date: 2018-08-24, release date: 2019-02-06, Last modification date: 2023-10-11) |
| Primary citation | Ng, T.L.,Rohac, R.,Mitchell, A.J.,Boal, A.K.,Balskus, E.P. An N-nitrosating metalloenzyme constructs the pharmacophore of streptozotocin. Nature, 566:94-99, 2019 Cited by PubMed Abstract: Small molecules containing the N-nitroso group, such as the bacterial natural product streptozotocin, are prominent carcinogens and important cancer chemotherapeutics. Despite the considerable importance of this functional group to human health, enzymes dedicated to the assembly of the N-nitroso unit have not been identified. Here we show that SznF, a metalloenzyme from the biosynthesis of streptozotocin, catalyses an oxidative rearrangement of the guanidine group of N-methyl-L-arginine to generate an N-nitrosourea product. Structural characterization and mutagenesis of SznF reveal two separate active sites that promote distinct steps in this transformation using different iron-containing metallocofactors. This biosynthetic reaction, which has little precedent in enzymology or organic synthesis, expands the catalytic capabilities of non-haem-iron-dependent enzymes to include N-N bond formation. We find that biosynthetic gene clusters that encode SznF homologues are widely distributed among bacteria-including environmental organisms, plant symbionts and human pathogens-which suggests an unexpectedly diverse and uncharacterized microbial reservoir of bioactive N-nitroso metabolites. PubMed: 30728519DOI: 10.1038/s41586-019-0894-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.69 Å) |
Structure validation
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