6M9S

Crystal structure of SeMet SznF from Streptomyces achromogenes var. streptozoticus NRRL 2697

6M9S の概要

• エントリーDOI: 10.2210/pdb6m9s/pdb
• 関連するPDBエントリー: 6M9R
• 分子名称: SznF, FE (III) ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: non-heme iron-dependent, cupin domain, helix bundle, monooxygenase, n-nitrosation, metal-bound, anaerobic, semet, selenemethionine, oxidoreductase
• 由来する生物種: Streptomyces achromogenes subsp. streptozoticus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 226253.72

構造登録者

Rohac, R.,Mitchell, A.J.,Boal, A.K. (登録日: 2018-08-24, 公開日: 2019-02-06, 最終更新日: 2024-11-13)

主引用文献

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

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: 30728519
DOI: 10.1038/s41586-019-0894-z

実験手法

X-RAY DIFFRACTION (2.08 Å)