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Publication Abstract from PubMed

Class II terpene cyclases, such as oxidosqualene and squalene-hopene cyclases, catalyse some of the most complex polycyclization reactions. They minimally exhibit a beta,gamma-didomain architecture that has been evolutionarily repurposed in a wide range of terpene-processing enzymes and likely resulted from a fusion of unidentified monodomain proteins. Although single domain class I terpene cyclases have already been identified, the corresponding class II counterparts have not been previously reported. Here we present high-resolution X-ray structures of a monodomain class II cyclase, merosterolic acid synthase (MstE). With a minimalistic beta-domain architecture, this cyanobacterial enzyme is able to construct four rings in cytotoxic meroterpenoids with a sterol-like topology. The structures with bound substrate, product, and inhibitor provide detailed snapshots of a cyclization mechanism largely governed by residues located in a noncanonical enzyme region. Our results complement the few known class II cyclase crystal structures, while also indicating that archaic monodomain cyclases might have already catalyzed complex reaction cascades.

A monodomain class II terpene cyclase assembles complex isoprenoid scaffolds.,Moosmann P, Ecker F, Leopold-Messer S, Cahn JKB, Dieterich CL, Groll M, Piel J Nat Chem. 2020 Aug 10. pii: 10.1038/s41557-020-0515-3. doi:, 10.1038/s41557-020-0515-3. PMID:32778689^[1]

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