Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC.

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.

authors

Ryan KS,Howard-Jones AR,Hamill MJ,Elliott SJ,Walsh CT,Drennan CL

doi

10.1073/pnas.0707190104

subject

Has Abstract

pub_date

2007-09-25 00:00:00

pages

15311-6

issue

39

eissn

0027-8424

issn

1091-6490

pii

0707190104

journal_volume

104

pub_type

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