Conformational switch triggered by [alpha]-ketoglutarate in a halogenase of curacin A biosynthesis
- Michigan
The CurA halogenase (Hal) catalyzes a cryptic chlorination leading to cyclopropane ring formation in the synthesis of the natural product curacin A. Hal belongs to a family of enzymes that use Fe{sup 2+}, O{sub 2} and {alpha}-ketoglutarate ({alpha}KG) to perform a variety of halogenation reactions in natural product biosynthesis. Crystal structures of the enzyme in five ligand states reveal strikingly different open and closed conformations dependent on {alpha}KG binding. The open form represents ligand-free enzyme, preventing substrate from entering the active site until both {alpha}KG and chloride are bound, while the closed form represents the holoenzyme with {alpha}KG and chloride coordinated to iron. Candidate amino acid residues involved in substrate recognition were identified by site-directed mutagenesis. These new structures provide direct evidence of a conformational switch driven by {alpha}KG leading to chlorination of an early pathway intermediate.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1002573
- Journal Information:
- Proc. Natl. Acad. Sci. USA, Vol. 107, Issue (32) ; 08, 2010; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- ENGLISH
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