2R0C

Structure of the substrate-free form of the rebeccamycin biosynthetic enzyme REBC

Summary for 2R0C

• Entry DOI: 10.2210/pdb2r0c/pdb
• Descriptor: RebC, CHLORIDE ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: flavin adenine dinucleotide, monooxygenase, oxidoreductase
• Biological source: Lechevalieria aerocolonigenes
• Total number of polymer chains: 1
• Total formula weight: 60748.63

Authors

Ryan, K.S.,Drennan, C.L. (deposition date: 2007-08-18, release date: 2007-09-25, Last modification date: 2024-02-21)

Primary citation

Ryan, K.S.,Howard-Jones, A.R.,Hamill, M.J.,Elliott, S.J.,Walsh, C.T.,Drennan, C.L.
Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC
Proc.Natl.Acad.Sci.Usa, 104:15311-15316, 2007

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.

PubMed: 17873060
DOI: 10.1073/pnas.0707190104

Experimental method

X-RAY DIFFRACTION (1.8 Å)