4XLO

Crystal Structure of EncM (crystallized with 4 mM NADPH)

Summary for 4XLO

• Entry DOI: 10.2210/pdb4xlo/pdb
• Related: 3W8W 3W8X 3W8Z
• Descriptor: FAD-dependent oxygenase EncM, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: flavoenzyme, nadph, vanillyl-alcohol oxidase/p-cresol methylhydroxylase fold, oxygenase, oxidoreductase
• Biological source: Streptomyces maritimus
• Total number of polymer chains: 4
• Total formula weight: 203439.68

Authors

Teufel, R. (deposition date: 2015-01-13, release date: 2015-01-28, Last modification date: 2024-10-23)

Primary citation

Teufel, R.,Miyanaga, A.,Michaudel, Q.,Stull, F.,Louie, G.,Noel, J.P.,Baran, P.S.,Palfey, B.,Moore, B.S.
Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement.
Nature, 503:552-556, 2013

PubMed Abstract: Flavoproteins catalyse a diversity of fundamental redox reactions and are one of the most studied enzyme families. As monooxygenases, they are universally thought to control oxygenation by means of a peroxyflavin species that transfers a single atom of molecular oxygen to an organic substrate. Here we report that the bacterial flavoenzyme EncM catalyses the peroxyflavin-independent oxygenation-dehydrogenation dual oxidation of a highly reactive poly(β-carbonyl). The crystal structure of EncM with bound substrate mimics and isotope labelling studies reveal previously unknown flavin redox biochemistry. We show that EncM maintains an unexpected stable flavin-oxygenating species, proposed to be a flavin-N5-oxide, to promote substrate oxidation and trigger a rare Favorskii-type rearrangement that is central to the biosynthesis of the antibiotic enterocin. This work provides new insight into the fine-tuning of the flavin cofactor in offsetting the innate reactivity of a polyketide substrate to direct its efficient electrocyclization.

PubMed: 24162851
DOI: 10.1038/nature12643

Experimental method

X-RAY DIFFRACTION (1.67 Å)