Crystallographic Trapping in the Rebeccamycin Biosynthetic Enzyme RebC
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.
- Research Organization:
- Stanford Linear Accelerator Center (SLAC)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC02-76SF00515
- OSTI ID:
- 953881
- Report Number(s):
- SLAC-REPRINT-2009-511
- Journal Information:
- Proc. Nat. Acad. Sci. 104:15311,2007, Journal Name: Proc. Nat. Acad. Sci. 104:15311,2007 Journal Issue: 39 Vol. 104; ISSN 0027-8424; ISSN PNASA6
- Country of Publication:
- United States
- Language:
- English
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