Structural highlights
Function
5EAS_TOBAC Catalyzes the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic intermediate 5-epi-aristolochene, initial step in the conversion of FPP to the sesquiterpenoid antifungal phytoalexin capsidiol. Produces germacrene A as an enzyme-bound intermediate that is not released by the enzyme, but is further cyclized to produce the bicyclic 5-epi-aristolochene.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Sesquiterpene skeletal complexity in nature originates from the enzyme-catalyzed ionization of (trans,trans)-farnesyl diphosphate (FPP) (1a) and subsequent cyclization along either 2,3-transoid or 2,3-cisoid farnesyl cation pathways. Tobacco 5-epi-aristolochene synthase (TEAS), a transoid synthase, produces cisoid products as a component of its minor product spectrum. To investigate the cryptic cisoid cyclization pathway in TEAS, we employed (cis,trans)-FPP (1b) as an alternative substrate. Strikingly, TEAS was catalytically robust in the enzymatic conversion of (cis,trans)-FPP (1b) to exclusively (>/=99.5%) cisoid products. Further, crystallographic characterization of wild-type TEAS and a catalytically promiscuous mutant (M4 TEAS) with 2-fluoro analogues of both all-trans FPP (1a) and (cis,trans)-FPP (1b) revealed binding modes consistent with preorganization of the farnesyl chain. These results provide a structural glimpse into both cisoid and transoid cyclization pathways efficiently templated by a single enzyme active site, consistent with the recently elucidated stereochemistry of the cisoid products. Further, computational studies using density functional theory calculations reveal concerted, highly asynchronous cyclization pathways leading to the major cisoid cyclization products. The implications of these discoveries for expanded sesquiterpene diversity in nature are discussed.
Structural Elucidation of Cisoid and Transoid Cyclization Pathways of a Sesquiterpene Synthase Using 2-Fluorofarnesyl Diphosphates.,Noel JP, Dellas N, Faraldos JA, Zhao M, Hess BA, Smentek L, Coates RM, O'Maille PE ACS Chem Biol. 2010 Mar 8. PMID:20175559[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Noel JP, Dellas N, Faraldos JA, Zhao M, Hess BA, Smentek L, Coates RM, O'Maille PE. Structural Elucidation of Cisoid and Transoid Cyclization Pathways of a Sesquiterpene Synthase Using 2-Fluorofarnesyl Diphosphates. ACS Chem Biol. 2010 Mar 8. PMID:20175559 doi:10.1021/cb900295g
