期刊
CHEMBIOCHEM
卷 15, 期 15, 页码 2259-2267出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201402241
关键词
aromatic nitration; crystal-structure determination; cytochromes; enzyme catalysis
资金
- Resnick Sustainability Institute (Caltech)
- Dow Chemical Company through Dow-Resnick innovation program
- Ruth L. Kirschstein NRSA from National Institutes of Health [5F32M106618, 5F32M101792]
- Swiss National Science Foundation [PBBSP2_146809]
- Gordon and Betty Moore Foundation
- Beckman Institute
- Sanofi-Aventis Bioengineering Research Program (Caltech)
- Swiss National Science Foundation (SNF) [PBBSP2_146809] Funding Source: Swiss National Science Foundation (SNF)
A novel cytochrome P450 enzyme, TxtE, was recently shown to catalyze the direct aromatic nitration of L-tryptophan. This unique chemistry inspired us to ask whether TxtE could serve as a platform for engineering new nitration biocatalysts to replace current harsh synthetic methods. As a first step toward this goal, and to better understand the wild-type enzyme, we obtained high-resolution structures of TxtE in its substrate-free and substrate-bound forms. We also screened a library of substrate analogues for spectroscopic indicators of binding and for production of nitrated products. From these results, we found that the wild-type enzyme accepts moderate decoration of the indole ring, but the amino acid moiety is crucial for binding and correct positioning of the substrate and therefore less amenable to modification. A nitrogen atom is essential for catalysis, and a carbonyl must be present to recruit the B-1 helix of the protein to seal the binding pocket.
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