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Phe36 Plays a Key Role in the Fluorine Recognition of Fluoroacetyl‐CoA Thioesterase FlK
Author(s) -
Wang Ningkun,
Pelton Jeffrey G.,
Chang Michelle C.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.527.3
Subject(s) - moiety , chemistry , stereochemistry , enzyme , substrate (aquarium) , ligand (biochemistry) , selectivity , fluorine , drug discovery , fluorine 19 nmr , thioesterase , biochemistry , nuclear magnetic resonance spectroscopy , biology , receptor , biosynthesis , organic chemistry , ecology , catalysis
Fluorinated small molecules play an important role in the design of bioactive compounds for a broad range of applications. Hence there is great interest in developing a deeper understanding of how proteins recognize fluorine moieties in ligands. The fluoroacetyl‐CoA thioesterase FlK from Streptomyces cattleya is one of the few enzymes that display a native selectivity towards organofluorine substrates, providing us a rare opportunity to study this enzyme‐ligand pair and the molecular interactions that lead to the 10 6 ‐fold selectivity for a single fluorine moiety. In this study, we have used protein NMR to dissect the molecular details of the interaction between FlK and substrate analogs. Previous studies have found that Phe36, a residue at the binding pocket of FlK, is important to the substrate specificity of the enzyme. Our work here shows that Phe36 displays a change in chemical shift specific to the binding of the fluoroacetyl‐CoA analog, and has determined that this discrimination between fluoroacetyl‐CoA and acetyl‐CoA analogs can be contributed to a decrease in exchange rate between the bound and free form of FlK as conveyed through Phe36. Support or Funding Information This work was funded by the generous support of the National Institutes of Health (R01 GM123181). The funds for the 900 MHz NMR spectrometer housed in the College of Chemistry NMR Facility at U.C. Berkeley were kindly provided by the NIH (GM68933). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .