| Structural highlights
Function
SZNF_STRC2 Involved in the biosynthesis of the glucosamine-nitrosourea antibiotic streptozotocin (SZN) (PubMed:30728519, PubMed:30763082). Catalyzes a complex multi-step reaction: the overall reaction is an oxidative rearrangement of the guanidine group of N(omega)-methyl-L-arginine (L-NMA), generating an N-nitrosourea product (PubMed:30728519, PubMed:30763082, PubMed:32511919). SznF first hydroxylates L-NMA to form N(delta)-hydroxy-N(omega)-methyl-L-arginine (L-HMA), which is further hydroxylated to give N(delta)-hydroxy-N(omega)-hydroxy-N(omega)-methyl-L-arginine (L-DHMA) (PubMed:30728519, PubMed:32511919). Subsequently, an oxidative rearrangement converts this intermediate to N(delta)-hydroxy-N(omega)-methyl-N(omega)-nitroso-L-citrulline (PubMed:30728519, PubMed:34004115). This product is unstable, and degrades non-enzymically into nitric oxide and the denitrosated product N(delta)-hydroxy-N(omega)-methyl-L-citrulline (PubMed:30728519).[1] [2] [3] [4]
References
- ↑ Ng TL, Rohac R, Mitchell AJ, Boal AK, Balskus EP. An N-nitrosating metalloenzyme constructs the pharmacophore of streptozotocin. Nature. 2019 Feb;566(7742):94-99. doi: 10.1038/s41586-019-0894-z. Epub 2019 Feb, 6. PMID:30728519 doi:https://dx.doi.org/10.1038/s41586-019-0894-z
- ↑ He HY, Henderson AC, Du YL, Ryan KS. Two-Enzyme Pathway Links l-Arginine to Nitric Oxide in N-Nitroso Biosynthesis. J Am Chem Soc. 2019 Mar 6;141(9):4026-4033. PMID:30763082 doi:10.1021/jacs.8b13049
- ↑ McBride MJ, Sil D, Ng TL, Crooke AM, Kenney GE, Tysoe CR, Zhang B, Balskus EP, Boal AK, Krebs C, Bollinger JM Jr. A Peroxodiiron(III/III) Intermediate Mediating Both N-Hydroxylation Steps in Biosynthesis of the N-Nitrosourea Pharmacophore of Streptozotocin by the Multi-domain Metalloenzyme SznF. J Am Chem Soc. 2020 Jul 8;142(27):11818-11828. PMID:32511919 doi:10.1021/jacs.0c03431
- ↑ Wang J, Wang X, Ouyang Q, Liu W, Shan J, Tan H, Li X, Chen G. N-Nitrosation Mechanism Catalyzed by Non-heme Iron-Containing Enzyme SznF Involving Intramolecular Oxidative Rearrangement. Inorg Chem. 2021 Jun 7;60(11):7719-7731. PMID:34004115 doi:10.1021/acs.inorgchem.1c00057
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