3nnj

Publication Abstract from PubMed

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(2+), O(2) and alpha-ketoglutarate (alphaKG) 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 alphaKG binding. The open form represents ligand-free enzyme, preventing substrate from entering the active site until both alphaKG and chloride are bound, while the closed form represents the holoenzyme with alphaKG 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 alphaKG leading to chlorination of an early pathway intermediate.

Conformational switch triggered by alpha-ketoglutarate in a halogenase of curacin A biosynthesis.,Khare D, Wang B, Gu L, Razelun J, Sherman DH, Gerwick WH, Hakansson K, Smith JL Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14099-104. Epub 2010 Jul 26. PMID:20660778^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.