In JoVE (1)

Other Publications (2)

Articles by Linda Chio in JoVE

Other articles by Linda Chio on PubMed

Exceedingly Efficient Synthesis of (±)-Grandifloracin and Acylated Analogues

Organic Letters. Jun, 2015  |  Pubmed ID: 26060887

A highly efficient regio- and stereoselective total synthesis of (±)-grandifloracin via a tandem dearomative epoxidation/spontaneous Diels-Alder cyclodimerization from salicylic acid in only four steps is reported. The synthetic route allows for late-stage diversification of the core structure to give ready access to analogues of this promising agent against pancreatic cancer.

Structural Adaptability Facilitates Histidine Heme Ligation in a Cytochrome P450

Journal of the American Chemical Society. Nov, 2015  |  Pubmed ID: 26299431

Almost all known members of the cytochrome P450 (CYP) superfamily conserve a key cysteine residue that coordinates the heme iron. Although mutation of this residue abolishes monooxygenase activity, recent work has shown that mutation to either serine or histidine unlocks non-natural carbene- and nitrene-transfer activities. Here we present the first crystal structure of a histidine-ligated P450. The T213A/C317H variant of the thermostable CYP119 from Sulfolobus acidocaldarius maintains heme iron coordination through the introduced ligand, an interaction that is accompanied by large changes in the overall protein structure. We also find that the axial cysteine C317 may be substituted with any other amino acid without abrogating folding and heme cofactor incorporation. Several of the axial mutants display unusual spectral features, suggesting that they have active sites with unique steric and electronic properties. These novel, highly stable enzyme active sites will be fruitful starting points for investigations of non-natural P450 catalysis and mechanisms.

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