ArticleBiochemistry2005
Role of arginine-304 in the diphosphate-triggered active site closure mechanism of trichodiene synthase.
Article in Biochemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 51 citations in OpenAlex.
- Article
- Engineering terpene synthases and their substrates for the biocatalytic production of terpene natural products and analogues.Chemical communications (Cambridge, England) · 2025Review
- Mechanistic docking in terpene synthases using EnzyDock.Methods in enzymology · 2024Review
- Signatures ofToxins · 2020Article
- Structural and Chemical Biology of Terpenoid Cyclases.Chemical reviews · 2017Review
- Chemical Control in the Battle against Fidelity in Promiscuous Natural Product Biosynthesis: The Case of Trichodiene Synthase.ACS catalysis · 2017Article
- Structure-based virtual screening of hypothetical inhibitors of the enzyme longiborneol synthase-a potential target to reduce Fusarium head blight disease.Journal of molecular modeling · 2016Article
- Identification of amino acid networks governing catalysis in the closed complex of class I terpene synthases.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Traversing the fungal terpenome.Natural product reports · 2014Review
- Predicting the functions and specificity of triterpenoid synthases: a mechanism-based multi-intermediate docking approach.PLoS computational biology · 2014Article
- Reprogramming the chemodiversity of terpenoid cyclization by remolding the active site contour of epi-isozizaene synthase.Biochemistry · 2014Article
- Terpenoid synthase structures: a so far incomplete view of complex catalysis.Natural product reports · 2012Review
- Selectivity of fungal sesquiterpene synthases: role of the active site's H-1 alpha loop in catalysis.Applied and environmental microbiology · 2010Article
- Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers.Chembiochem : a European journal of chemical biology · 2010Article
- Structural elucidation of cisoid and transoid cyclization pathways of a sesquiterpene synthase using 2-fluorofarnesyl diphosphates.ACS chemical biology · 2010Article
- Trinuclear Metal Clusters in Catalysis by Terpenoid Synthases.Pure and applied chemistry. Chimie pure et appliquee · 2010Article
- Structural and mechanistic analysis of trichodiene synthase using site-directed mutagenesis: probing the catalytic function of tyrosine-295 and the asparagine-225/serine-229/glutamate-233-Mg2+B motif.Archives of biochemistry and biophysics · 2008Article
- Exploring biosynthetic diversity with trichodiene synthase.Archives of biochemistry and biophysics · 2007Article
- X-ray crystal structure of aristolochene synthase from Aspergillus terreus and evolution of templates for the cyclization of farnesyl diphosphate.Biochemistry · 2007Article
- Mechanisms and free energies of enzymatic reactions.Chemical reviews · 2006Review
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
The X-ray crystal structures of R304K trichodiene synthase and its complexes with inorganic pyrophosphate (PP(i)) and aza analogues of the bisabolyl carbocation intermediate are reported. The R304K substitution does not cause large changes in the overall structure in comparison with the wild-type enzyme. The complexes with (R)- and (S)-azabisabolenes and PP(i) bind three Mg2+ ions, and each undergoes a diphosphate-triggered conformational change that caps the active site cavity. This conformational change is only slightly attenuated compared to that of the wild-type enzyme complexed with Mg2+(3)-PP(i), in which R304 donates hydrogen bonds to PP(i) and D101. In R304K trichodiene synthase, K304 does not engage in any hydrogen bond interactions in the unliganded state and it donates a hydrogen bond to only PP(i) in the complex with (R)-azabisabolene; K304 makes no hydrogen bond contacts in its complex with PP(i) and (S)-azabisabolene. Thus, although the R304-D101 hydrogen bond interaction stabilizes diphosphate-triggered active site closure, it is not required for Mg2+(3)-PP(i) binding. Nevertheless, since R304K trichodiene synthase generates aberrant cyclic terpenoids with a 5000-fold reduction in kcat/KM, it is clear that a properly formed R304-D101 hydrogen bond is required in the enzyme-substrate complex to stabilize the proper active site contour, which in turn facilitates cyclization of farnesyl diphosphate for the exclusive formation of trichodiene. Structural analysis of the R304K mutant and comparison with the monoterpene cyclase (+)-bornyl diphosphate synthase suggest that the significant loss in activity results from compromised activation of the PP(i) leaving group.
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