6FOW

The crystal structure of EncM complexed with dioxygen under 10 bar of oxygen pressure.

Summary for 6FOW

• Entry DOI: 10.2210/pdb6fow/pdb
• Descriptor: Putative FAD-dependent oxygenase EncM, FLAVIN-ADENINE DINUCLEOTIDE, OXYGEN MOLECULE, ... (4 entities in total)
• Functional Keywords: monooxygenase, flavin-n5-oxide, fad, encm, oxygenating species, oxygen binding, flavoprotein
• Biological source: Streptomyces maritimus
• Total number of polymer chains: 4
• Total formula weight: 203567.68

Authors

Saleem-Batcha, R.,Teufel, R. (deposition date: 2018-02-08, release date: 2018-05-02, Last modification date: 2024-02-07)

Primary citation

Saleem-Batcha, R.,Stull, F.,Sanders, J.N.,Moore, B.S.,Palfey, B.A.,Houk, K.N.,Teufel, R.
Enzymatic control of dioxygen binding and functionalization of the flavin cofactor.
Proc. Natl. Acad. Sci. U.S.A., 115:4909-4914, 2018

PubMed Abstract: The reactions of enzymes and cofactors with gaseous molecules such as dioxygen (O) are challenging to study and remain among the most contentious subjects in biochemistry. To date, it is largely enigmatic how enzymes control and fine-tune their reactions with O, as exemplified by the ubiquitous flavin-dependent enzymes that commonly facilitate redox chemistry such as the oxygenation of organic substrates. Here we employ O-pressurized X-ray crystallography and quantum mechanical calculations to reveal how the precise positioning of O within a flavoenzyme's active site enables the regiospecific formation of a covalent flavin-oxygen adduct and oxygenating species (i.e., the flavin-N5-oxide) by mimicking a critical transition state. This study unambiguously demonstrates how enzymes may control the O functionalization of an organic cofactor as prerequisite for oxidative catalysis. Our work thus illustrates how O reactivity can be harnessed in an enzymatic environment and provides crucial knowledge for future rational design of O-reactive enzymes.

PubMed: 29686059
DOI: 10.1073/pnas.1801189115

Experimental method

X-RAY DIFFRACTION (2.04 Å)