期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 19, 页码 4909-4914出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1801189115
关键词
monooxygenase; EncM; FAD; flavin-N5-oxide; bioengineering
资金
- Deutsche Forschungsgemeinschaft [TE 931/2-1]
- National Institute of General Medical Sciences of the National Institutes of Health (NIH) [F32GM122218]
- US National Science Foundation (NSF) [CHE-1361104]
- NIH [R01-AI47818]
- NSF [OCI-1053575]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI047818] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [F32GM122218] Funding Source: NIH RePORTER
The reactions of enzymes and cofactors with gaseous molecules such as dioxygen (O-2) 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-2, as exemplified by the ubiquitous flavin-dependent enzymes that commonly facilitate redox chemistry such as the oxygenation of organic substrates. Here we employ O-2-pressurized X-ray crystallography and quantum mechanical calculations to reveal how the precise positioning of O-2 within a flavoenzyme's active site enables the regio-specific 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-2 functionalization of an organic cofactor as prerequisite for oxidative catalysis. Our work thus illustrates how O-2 reactivity can be harnessed in an enzymatic environment and provides crucial knowledge for future rational design of O-2-reactive enzymes.
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