4XAB

Crystal Structure of EvdO2 from Micromonospora carbonacea var. aurantiaca

4XAB の概要

• エントリーDOI: 10.2210/pdb4xab/pdb
• 関連するPDBエントリー: 4XAA 4XAC
• 分子名称: EvdO2, NICKEL (II) ION, IMIDAZOLE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, double stranded beta helix
• 由来する生物種: Micromonospora carbonacea
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28808.03

構造登録者

McCulloch, K.M.,McCranie, E.K.,Sarwar, M.,Mathieu, J.L.,Gitschlag, B.L.,Du, Y.,Bachmann, B.O.,Iverson, T.M. (登録日: 2014-12-13, 公開日: 2015-08-05, 最終更新日: 2023-09-27)

主引用文献

McCulloch, K.M.,McCranie, E.K.,Smith, J.A.,Sarwar, M.,Mathieu, J.L.,Gitschlag, B.L.,Du, Y.,Bachmann, B.O.,Iverson, T.M.
Oxidative cyclizations in orthosomycin biosynthesis expand the known chemistry of an oxygenase superfamily.
Proc.Natl.Acad.Sci.USA, 112:11547-11552, 2015

PubMed Abstract: Orthosomycins are oligosaccharide antibiotics that include avilamycin, everninomicin, and hygromycin B and are hallmarked by a rigidifying interglycosidic spirocyclic ortho-δ-lactone (orthoester) linkage between at least one pair of carbohydrates. A subset of orthosomycins additionally contain a carbohydrate capped by a methylenedioxy bridge. The orthoester linkage is necessary for antibiotic activity but rarely observed in natural products. Orthoester linkage and methylenedioxy bridge biosynthesis require similar oxidative cyclizations adjacent to a sugar ring. We have identified a conserved group of nonheme iron, α-ketoglutarate-dependent oxygenases likely responsible for this chemistry. High-resolution crystal structures of the EvdO1 and EvdO2 oxygenases of everninomicin biosynthesis, the AviO1 oxygenase of avilamycin biosynthesis, and HygX of hygromycin B biosynthesis show how these enzymes accommodate large substrates, a challenge that requires a variation in metal coordination in HygX. Excitingly, the ternary complex of HygX with cosubstrate α-ketoglutarate and putative product hygromycin B identified an orientation of one glycosidic linkage of hygromycin B consistent with metal-catalyzed hydrogen atom abstraction from substrate. These structural results are complemented by gene disruption of the oxygenases evdO1 and evdMO1 from the everninomicin biosynthetic cluster, which demonstrate that functional oxygenase activity is critical for antibiotic production. Our data therefore support a role for these enzymes in the production of key features of the orthosomycin antibiotics.

PubMed: 26240321
DOI: 10.1073/pnas.1500964112

実験手法

X-RAY DIFFRACTION (1.75 Å)