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Publication Abstract from PubMed

The natural product curacin A, a potent anticancer agent, contains a rare cyclopropane group. The five enzymes for cyclopropane biosynthesis are highly similar to enzymes that generate a vinyl chloride moiety in the jamaicamide natural product. The structural biology of this remarkable catalytic adaptability is probed with high-resolution crystal structures of the curacin cyclopropanase (CurF ER), an in vitro enoyl reductase (JamJ ER), and a canonical curacin enoyl reductase (CurK ER). The JamJ and CurK ERs catalyze NADPH-dependent double bond reductions typical of enoyl reductases (ERs) of the medium-chain dehydrogenase reductase (MDR) superfamily. Cyclopropane formation by CurF ER is specified by a short loop which, when transplanted to JamJ ER, confers cyclopropanase activity on the chimeric enzyme. Detection of an adduct of NADPH with the model substrate crotonyl-CoA provides indirect support for a recent proposal of a C2-ene intermediate on the reaction pathway of MDR enoyl-thioester reductases.

Structural Basis for Cyclopropanation by a Unique Enoyl-Acyl Carrier Protein Reductase.,Khare D, Hale WA, Tripathi A, Gu L, Sherman DH, Gerwick WH, Hakansson K, Smith JL Structure. 2015 Oct 24. pii: S0969-2126(15)00405-0. doi:, 10.1016/j.str.2015.09.013. PMID:26526850^[1]

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