title: Induced-fit mechanism in class I terpene cyclases.
abstract: We present crystallographic and functional data of selina-4(15),7(11)-diene synthase (SdS) from Streptomyces pristinaespiralis in its open and closed (ligand-bound) conformation. We could identify an induced-fit mechanism by elucidating a rearrangement of the G1/2 helix-break motif upon substrate binding. This rearrangement highlights a novel effector triad comprising the pyrophosphate sensor Arg178, the linker Asp181, and the effector Gly182-O. This structural motif is strictly conserved in class I terpene cyclases from bacteria, fungi, and plants, including epi-isozizaene synthase (3KB9), aristolochene synthase (4KUX), bornyl diphosphate synthase (1N20), limonene synthase (2ONG), 5-epi-aristolochene synthase (5EAT), and taxa-4(5),11(12)-diene synthase (3P5R). An elaborate structure-based mutagenesis in combination with analysis of the distinct product spectra confirmed the mechanistic models of carbocation formation and stabilization in SdS.
authors.affiliation: Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, TU München (Germany).
authors.forename: Philipp
authors.initials: P
authors.lastname: Baer
authors.forename: Patrick
authors.initials: P
authors.lastname: Rabe
authors.forename: Katrin
authors.initials: K
authors.lastname: Fischer
authors.forename: Christian A
authors.initials: CA
authors.lastname: Citron
authors.forename: Tim A
authors.initials: TA
authors.lastname: Klapschinski
authors.forename: Michael
authors.initials: M
authors.lastname: Groll
authors.forename: Jeroen S
authors.initials: JS
authors.lastname: Dickschat
mesh_terms: D004798:Enzymes / Q000737:chemistry*; D008958:Models, Molecular; D013729:Terpenes / Q000737:chemistry*
chemical_list: D004798:Enzymes; D013729:Terpenes
keywords: biosynthesis; carbocations; enzyme models; pyrophosphate sensor; terpenoids