Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC.
Article Details
- CitationCopy to clipboard
Ryan KS, Howard-Jones AR, Hamill MJ, Elliott SJ, Walsh CT, Drennan CL
Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC.
Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15311-6. Epub 2007 Sep 14.
- PubMed ID
- 17873060 [ View in PubMed]
- Abstract
The biosynthesis of rebeccamycin, an antitumor compound, involves the remarkable eight-electron oxidation of chlorinated chromopyrrolic acid. Although one rebeccamycin biosynthetic enzyme is capable of generating low levels of the eight-electron oxidation product on its own, a second protein, RebC, is required to accelerate product formation and eliminate side reactions. However, the mode of action of RebC was largely unknown. Using crystallography, we have determined a likely function for RebC as a flavin hydroxylase, captured two snapshots of its dynamic catalytic cycle, and trapped a reactive molecule, a putative substrate, in its binding pocket. These studies strongly suggest that the role of RebC is to sequester a reactive intermediate produced by its partner protein and to react with it enzymatically, preventing its conversion to a suite of degradation products that includes, at low levels, the desired product.