5WGR

Crystal Structure of Wild-type MalA', premalbrancheamide complex

5WGR の概要

• エントリーDOI: 10.2210/pdb5wgr/pdb
• 分子名称: Flavin-dependent halogenase, FLAVIN-ADENINE DINUCLEOTIDE, CADMIUM ION, ... (8 entities in total)
• 機能のキーワード: flavin-dependent halogenase, malbrancheamide, zinc, zn, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Malbranchea aurantiaca
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 76992.62

構造登録者

Fraley, A.E.,Smith, J.L. (登録日: 2017-07-14, 公開日: 2017-08-16, 最終更新日: 2023-10-04)

主引用文献

Fraley, A.E.,Garcia-Borras, M.,Tripathi, A.,Khare, D.,Mercado-Marin, E.V.,Tran, H.,Dan, Q.,Webb, G.P.,Watts, K.R.,Crews, P.,Sarpong, R.,Williams, R.M.,Smith, J.L.,Houk, K.N.,Sherman, D.H.
Function and Structure of MalA/MalA', Iterative Halogenases for Late-Stage C-H Functionalization of Indole Alkaloids.
J. Am. Chem. Soc., 139:12060-12068, 2017

PubMed Abstract: Malbrancheamide is a dichlorinated fungal indole alkaloid isolated from both Malbranchea aurantiaca and Malbranchea graminicola that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core. The introduction of chlorine atoms on the indole ring of malbrancheamide differentiates it from other members of this family and contributes significantly to its biological activity. In this study, we characterized the two flavin-dependent halogenases involved in the late-stage halogenation of malbrancheamide in two different fungal strains. MalA and MalA' catalyze the iterative dichlorination and monobromination of the free substrate premalbrancheamide as the final steps in the malbrancheamide biosynthetic pathway. Two unnatural bromo-chloro-malbrancheamide analogues were generated through MalA-mediated chemoenzymatic synthesis. Structural analysis and computational studies of MalA' in complex with three substrates revealed that the enzyme represents a new class of zinc-binding flavin-dependent halogenases and provides new insights into a potentially unique reaction mechanism.

PubMed: 28777910
DOI: 10.1021/jacs.7b06773

実験手法

X-RAY DIFFRACTION (2.362 Å)