ArticleProceedings of the National Academy of Sciences of the United States of America1994
Yeast farnesyl-diphosphate synthase: site-directed mutagenesis of residues in highly conserved prenyltransferase domains I and II.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 180 citations in OpenAlex.
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- Systematic characterization and functional analysis ofFrontiers in plant science · 2025Article
- A cytosolic bifunctional geranyl/farnesyl diphosphate synthase provides MVA-derived GPP for geraniol biosynthesis in rose flowers.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The catalytic and structural basis of archaeal glycerophospholipid biosynthesis.Extremophiles : life under extreme conditions · 2022Review
- Rational design of Lepidoptera-specific insecticidal inhibitors targeting farnesyl diphosphate synthase, a key enzyme of the juvenile hormone biosynthetic pathway.Journal of pesticide science · 2021Article
- Identifying Structural Determinants of Product Specificity inBiochemistry · 2020Article
- Crystal Structure of Geranylgeranyl Pyrophosphate Synthase (CrtE) Involved in Cyanobacterial Terpenoid Biosynthesis.Frontiers in plant science · 2020Article
- Phosphonate and Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthases: A Structure-Guided Perspective.Frontiers in chemistry · 2020Review
- Functional Gene Network of Prenyltransferases inMolecules (Basel, Switzerland) · 2019Review
- Computational design of a modular protein sense-response system.Science (New York, N.Y.) · 2019Article
- Molecular cloning and functional characterization of multiple geranylgeranyl pyrophosphate synthases (ApGGPPS) from Andrographis paniculata.Plant cell reports · 2019Article
- Structural and Chemical Biology of Terpenoid Cyclases.Chemical reviews · 2017Review
- Identification of geranylgeranyl diphosphate synthase genes from Tripterygium wilfordii.Plant cell reports · 2015Article
- Functional Characterization of Novel Sesquiterpene Synthases from Indian Sandalwood, Santalum album.Scientific reports · 2015Article
- Structural characterization of substrate and inhibitor binding to farnesyl pyrophosphate synthase from Pseudomonas aeruginosa.Acta crystallographica. Section D, Biological crystallography · 2015Article
- Article
- Proposed carrier lipid-binding site of undecaprenyl pyrophosphate phosphatase from Escherichia coli.The Journal of biological chemistry · 2014Article
- Geranylgeranyl reductase and ferredoxin from Methanosarcina acetivorans are required for the synthesis of fully reduced archaeal membrane lipid in Escherichia coli cells.Journal of bacteriology · 2014Article
- Human isoprenoid synthase enzymes as therapeutic targets.Frontiers in chemistry · 2014Review
- Article
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2 authors at 1 institution in 1 country.
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Abstract
Prenyltransferases that catalyze the fundamental chain elongation reaction in the isoprenoid biosynthetic pathway contain several highly conserved amino acids, including two aspartate-rich regions thought to be involved in substrate binding and catalysis. We report a study of site-directed mutants for yeast farnesyl-diphosphate synthase (FPPSase; geranyl-diphosphate:isopentenyl-diphosphate, EC 2.5.1.10), a prenyltransferase that catalyzes the sequential 1'-4 coupling of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate and geranyl diphosphate. A recombinant form of FPPSase extended by a C-terminal -Glu-Glu-Phe alpha-tubulin epitope (EEF in single-letter amino acid code) was engineered to facilitate rapid purification of the enzyme by immunoaffinity chromatography and to remove traces of contaminating activity from wild-type FPPSase in the Escherichia coli host. Ten site-directed mutants were constructed in FPPSase::EEF. The six aspartates in domain I (at positions 100, 101, and 104) and domain II (at positions 240, 241, and 244) were changed to alanine (mutants designated D100A, D101A, D104A, D240A, D241A, and D244A); three arginine residues were changed, Arg-109 and Arg-110 to glutamine and Arg-350 to alanine (mutants designated R109Q, R110Q, and R350A); and Lys-254 was converted to alanine (mutant designated K254A). Mutations of the aspartatic residues and nearby arginine residues in domain I and Asp-240 and Asp-241 in domain II drastically lowered the catalytic activity of FPPSase::EEF. The D244A and K254A mutants were substantially less active, while kcat and the Michaelis constants for the R350A mutant were similar to those of FPPSase::EEF. Addition of an -EEF epitope to the C terminus of wild-type FPPSase resulted in a 14-fold increase of KmIPP and a 12-fold decrease of kcat, suggesting that the conserved hydrophilic C terminus of the enzyme may have a role in substrate binding and catalysis.
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