It has long been known that small changes to the structure of R(2) side chain nitrogen-containing bisphosphonates can dramatically affect their potency for inhibiting bone resorption in vitro and vivo, although reason these differences antiresorptive have not explained at level a pharmacological target. Recently, several were found inhibit osteoclast-mediated by farnesyl diphosphate synthase, thereby preventing protein prenylation osteoclasts. In this study, we examined wider range...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystal Structure of Recombinant Farnesyl Diphosphate Synthase at 2.6-.ANG. ResolutionL. C. Tarshis, Mujing Yan, Dale Poulter, and James SacchettiniCite this: Biochemistry 1994, 33, 36, 10871–10877Publication Date (Print):September 13, 1994Publication History Published online1 May 2002Published inissue 13 September 1994https://pubs.acs.org/doi/10.1021/bi00202a004https://doi.org/10.1021/bi00202a004research-articleACS PublicationsRequest reuse...

An analysis of the x-ray structure homodimeric avian farnesyl diphosphate synthase (geranyltransferase, EC 2.5.1.10 ) coupled with information about conserved amino acids obtained from a sequence alignment 35 isoprenyl synthases that synthesize (C 15 ), geranylgeranyl 20 and higher chain length isoprenoid diphosphates suggested side chains residues corresponding to F112 F113 in enzyme were important for determining ultimate hydrocarbon chains. This hypothesis was supported by site-directed...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphorylation of isoprenoid alcoholsV. Jo Davisson, Andrew B. Woodside, Timothy R. Neal, Kay E. Stremler, Manfred Muehlbacher, and C. Dale PoulterCite this: J. Org. Chem. 1986, 51, 25, 4768–4779Publication Date (Print):December 1, 1986Publication History Published online1 May 2002Published inissue 1 December 1986https://pubs.acs.org/doi/10.1021/jo00375a005https://doi.org/10.1021/jo00375a005research-articleACS PublicationsRequest reuse...

Abstract Isoprenyl diphosphate synthases are ubiquitous enzymes that catalyze the basic chain‐elongation reaction in isoprene biosynthetic pathway. Pairwise sequence comparisons were made for 6 farnesyl synthases, geranylgeranyl and a hexaprenyl synthase. Five regions with highly conserved residues, two of which contain aspartate‐rich DDXX(XX)D motifs found many prenyltransferases, identified. A consensus secondary structure group, consisting mostly α‐helices, was predicted multiply aligned...

The carbon skeletons of over 55,000 naturally occurring isoprenoid compounds are constructed from four fundamental coupling reactions: chain elongation, cyclopropanation, branching, and cyclobutanation. Enzymes that catalyze elongation cyclopropanation well studied, whereas those branching cyclobutanation unknown. We have catalyzed the reactions with chimeric proteins generated by replacing segments a chain-elongation enzyme corresponding sequences enzyme. Stereochemical mechanistic...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe prenyl transfer reaction. Enzymic and mechanistic studies of the 1'-4 coupling reaction in terpene biosynthetic pathwayC. Dale Poulter Hans C. RillingCite this: Acc. Chem. Res. 1978, 11, 8, 307–313Publication Date (Print):August 1, 1978Publication History Published online1 May 2002Published inissue 1 August 1978https://pubs.acs.org/doi/10.1021/ar50128a004https://doi.org/10.1021/ar50128a004research-articleACS PublicationsRequest reuse...

Prenyltransferases that catalyze the fundamental chain elongation reaction in isoprenoid biosynthetic pathway contain several highly conserved amino acids, including two aspartate-rich regions thought to be involved 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), prenyltransferase catalyzes sequential 1'-4 coupling isopentenyl diphosphate (IPP) with...

The post-translational processing of the yeast a-mating pheromone precursor, Ras proteins, nuclear lamins, and some subunits trimeric G proteins requires a set complex modifications at their carboxyl termini. This includes three steps: prenylation cysteine residue, proteolytic processing, carboxymethylation. In Saccharomyces cerevisiae , product DPR1-RAM1 gene participates in this type processing. Through use an vitro assay with peptide substrates modeled after presumptive it was discovered...

Farnesyl diphosphate (FPP) synthetase is a key enzyme in isoprenoid biosynthesis which supplies C15 precursors for several classes of essential metabolites including sterols, dolichols, and ubiquinones. The structural gene FPP was isolated on 4.5-kilobase EcoRI genomic restriction fragment from the yeast Saccharomyces cerevisiae. clone encodes 40,483-dalton polypeptide 342 amino acids with high degree similarity to protein encoded by putative rat liver (Clarke, C. F., Tanaka, R. D., Svenson,...

ABSTRACT Isopentenyl diphosphate isomerase catalyzes the interconversion of isopentenyl (IPP) and dimethylallyl (DMAPP). In eukaryotes, archaebacteria, some bacteria, IPP is synthesized from acetyl coenzyme A by mevalonate pathway. The subsequent isomerization to DMAPP activates five-carbon isoprene unit for prenyl transfer reactions. Escherichia coli , pyruvate glyceraldehyde-3-phosphate recently discovered nonmevalonate An open reading frame (ORF696) encoding a putative was identified in...

A general approach was developed for the regio- and chemoselective covalent immobilization of soluble proteins on glass surfaces through an unnatural amino acid created by post-translationally modifying cysteine residue in a CaaX recognition motif with functional groups suitable "click" chemistry or Staudinger ligation. Farnesyl diphosphate analogues bearing ω-azide ω-alkyne moieties were attached to Cys-Val-Ile-Ala motifs at C-termini engineered versions green fluorescent protein (GFP)...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of nucleotide 5'-diphosphates from 5'-O-tosyl nucleosidesV. Jo Davisson, Darrell R. Davis, Vyas M. Dixit, and C. Dale PoulterCite this: J. Org. Chem. 1987, 52, 9, 1794–1801Publication Date (Print):May 1, 1987Publication History Published online1 May 2002Published inissue 1 1987https://pubs.acs.org/doi/10.1021/jo00385a026https://doi.org/10.1021/jo00385a026research-articleACS PublicationsRequest reuse permissionsArticle...

2-C-Methyl-D-erythritol-4-phosphate synthase (MEP synthase) catalyzes the rearrangement/reduction of 1-D-deoxyxylulose-5-phosphate (DXP) to methylerythritol-4-phosphate (MEP) as first pathway-specific reaction in MEP biosynthetic pathway isoprenoids. Recombinant E. coli was purified by chromatography on DE-52 and phenyl-Sepharose, its steady-state kinetic constants were determined: k(cat) = 116 +/- 8 s(-1), K(M)(DXP) 115 25 microM, K(M)(NADPH) 0.5 0.2 microM. The is reversible; K(eq) 45 6...

Comparison of the farnesyl diphosphate (FPP) synthase amino acid sequences from four species with related enzymes hexaprenyl and geranylgeranyl show presence two aspartate rich highly conserved domains.The motif ((I, L, or V)XDDXXD) second those domains has homology at least 9 prenyl transfer that utilize an allylic as one substrate.In order to investigate role this aspartaterich domain in rat FPP synthase, we mutated first third glutamate, expressed wildtype mutant Escherichia coli,...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiosynthesis of non-head-to-tail terpenes. Formation 1'-1 and 1'-3 linkagesC. Dale PoulterCite this: Acc. Chem. Res. 1990, 23, 3, 70–77Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/ar00171a003https://doi.org/10.1021/ar00171a003research-articleACS PublicationsRequest reuse permissionsArticle Views681Altmetric-Citations105LEARN ABOUT THESE...

Squalene (SQ) is an intermediate in the biosynthesis of sterols eukaryotes and a few bacteria hopanoids where they promote membrane stability formation lipid rafts their hosts. The genes for hopanoid are typically located on clusters that consist four highly conserved genes-hpnC, hpnD, hpnE, hpnF-for conversion farnesyl diphosphate (FPP) to hopene or related pentacyclic metabolites. While hpnF known encode squalene cyclase, functions hpnC, hpnE not rigorously established. from Zymomonas...

Significance This paper reports a large-scale collaborative study of an approach for predicting the function chain elongation prenyltransferases from genetic data. A diverse set genes enzymes in isoprenoid synthase superfamily was identified cloning, expression, X-ray structural analysis, and prediction by docking to homology models. Blind predictions, later verified biochemically, were accurate within one isoprene unit all but few 74 studied, extraordinarily high level given that often give...

Chrysanthemyl diphosphate synthase (CPPase) catalyzes the condensation of two molecules dimethylallyl to produce chrysanthemyl (CPP), a monoterpene with non-head-to-tail or irregular c1'-2-3 linkage between isoprenoid units. Irregular monoterpenes are common in Chrysanthemum cinerariaefolium and related members Asteraceae family. In C. cinerariaefolium, CPP is an intermediate biosynthesis pyrethrin ester insecticides. CPPase was purified from immature chrysanthemum flowers, N terminus...

Many proteins that contain a carboxyl-terminal CaaX sequence motif, including Ras and yeast a-factor, undergo series of sequential posttranslational processing steps. Following the initial prenylation cysteine, three C-terminal amino acids are proteolytically removed, newly formed prenylcysteine is carboxymethylated. The specific comprise influence whether protein can be prenylated proteolyzed. In this study, we evaluated a-factor variants with all possible single acid substitutions at...