Crystal Structure of Recombinant Farnesyl Diphosphate Synthase at 2.6-.ANG. Resolution

Tarshis, L.C; Yan, Ming; Poulter, C. Dale; Sacchettini, James C.

doi:10.1021/bi00202a004

Cited by 417 publications

(467 citation statements)

References 21 publications

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“…Second, the pyrophosphorylation shows an absolute requirement for divalent cations, with Mg 2ϩ preferred (18). Both of these features are reminiscent of the prenyl diphosphate synthases, which feature DDXXD motifs that coordinate Mg 2ϩ , which in turn activates the pyrophosphate as a leaving group (22). For serine pyrophosphorylation, one can imagine IP 7 phosphates organized by H-bonds within a polySer tract, whereas the IP 7 pyrophosphate could be activated and targeted to a particular phosphoserine phosphate with the assistance of an Asp/Glu-chelated Mg 2ϩ .…”

mentioning

confidence: 99%

Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event

Bhandari

Saiardi

Ahmadibeni

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

207

307

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The authors note that Figs. 1b, 1d, 1g, and 4a have been revised to include dividing lines between lanes to show where nonessential lanes were removed from a single original gel. Figs. 2c, 2d, and 3c have been revised to include boxes to indicate samples run on different gels, under the same conditions; these gels are aligned with respect to the indicated molecular weight markers. Figs. 4b and 4c have been revised to eliminate errors that occurred in the original version during file conversion. The changes were made to comply with the PNAS policy that requires dividing lines whenever entire nonessential lanes have been removed from a single original gel, and clear demarcation of samples run on separate gels. These changes do not affect the data presented nor the conclusions of the article. The corrected figures and their legends appear below.

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mentioning

confidence: 99%

Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event

Bhandari

Saiardi

Ahmadibeni

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

207

307

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“…Most of the prenyl transferases accept DMADP as the initial substrate, but they also bind GDP or FDP depending on the particular prenyltransferase (Greenhagen and Chappell, 2001;Tarshis et al, 1994Tarshis et al, , 1996Withers and Keasling, 2007). The availability of GDP and FDP are often the key factor in the production of monoterpenes and sesquiterpenes in plants.…”

Section: Carbohydrate-derived Flavor Compoundsmentioning

confidence: 99%

Biosynthesis of plant‐derived flavor compounds

Schwab¹,

Davidovich‐Rikanati²,

Lewinsohn³

2008

The Plant Journal

968

704

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SummaryPlants have the capacity to synthesize, accumulate and emit volatiles that may act as aroma and flavor molecules due to interactions with human receptors. These low-molecular-weight substances derived from the fatty acid, amino acid and carbohydrate pools constitute a heterogenous group of molecules with saturated and unsaturated, straight-chain, branched-chain and cyclic structures bearing various functional groups (e.g. alcohols, aldehydes, ketones, esters and ethers) and also nitrogen and sulfur. They are commercially important for the food, pharmaceutical, agricultural and chemical industries as flavorants, drugs, pesticides and industrial feedstocks. Due to the low abundance of the volatiles in their plant sources, many of the natural products had been replaced by their synthetic analogues by the end of the last century. However, the foreseeable shortage of the crude oil that is the source for many of the artifical flavors and fragrances has prompted recent interest in understanding the formation of these compounds and engineering their biosynthesis. Although many of the volatile constituents of flavors and aromas have been identified, many of the enzymes and genes involved in their biosynthesis are still not known. However, modification of flavor by genetic engineering is dependent on the knowledge and availability of genes that encode enzymes of key reactions that influence or divert the biosynthetic pathways of plant-derived volatiles. Major progress has resulted from the use of molecular and biochemical techniques, and a large number of genes encoding enzymes of volatile biosynthesis have recently been reported.

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“…OPPs is a trans-type enzyme synthesizing the C 40 long chain product. The only other transtype enzyme with known structure is FPPs of the short chain type (15). Based on its three-dimensional structure and mutagenesis studies, a bulky amino acid residue located in the fifth position before the first DDXXD motif of FPPs appeared to block further elongation of the product FPP (16).…”

mentioning

confidence: 99%

Crystal Structure of Octaprenyl Pyrophosphate Synthase from Hyperthermophilic Thermotoga maritima and Mechanism of Product Chain Length Determination

Guo

Kuo

Chou

et al. 2004

Journal of Biological Chemistry

111

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Octaprenyl pyrophosphate synthase (OPPs) catalyzes consecutive condensation reactions of farnesyl pyrophosphate (FPP) with isopentenyl pyrophosphate (IPP) to generate C 40 octaprenyl pyrophosphate (OPP), which constitutes the side chain of bacterial ubiquinone or menaquinone. In this study, the first structure of long chain C 40 -OPPs from Thermotoga maritima has been determined to 2.28-Å resolution. OPPs is composed entirely of ␣-helices joined by connecting loops and is arranged with nine core helices around a large central cavity. An elongated hydrophobic tunnel between D and F ␣-helices contains two DDXXD motifs on the top for substrate binding and is occupied at the bottom with two large residues Phe-52 and Phe-132. The products of the mutant F132A OPPs are predominantly C 50 , longer than the C 40 synthesized by the wild-type and F52A mutant OPPs, suggesting that Phe-132 is the key residue for determining the product chain length. Ala-76 and Ser-77 located close to the FPP binding site and Val-73 positioned further down the tunnel were individually mutated to larger amino acids. A76Y and S77F mainly produce C 20 indicating that the mutated large residues in the vicinity of the FPP site limit the substrate chain elongation. Ala-76 is the fifth amino acid upstream from the first DDXXD motif on helix D of OPPs, and its corresponding amino acid in FPPs is Tyr. In contrast, V73Y mutation led to additional accumulation of C 30 intermediate. The new structure of the trans-type OPPs, together with the recently determined cis-type UPPs, significantly extends our understanding on the biosynthesis of long chain polyprenyl molecules.Prenyltransferases catalyze consecutive condensation reactions of isopentenyl pyrophosphate (IPP) 1 with allylic pyrophosphate to generate linear isoprenyl polymers (1-3). Starting from IPP and its isomer dimethylallyl pyrophosphate, the C 15 farnesyl pyrophosphate (FPP) is formed by farnesyl pyrophosphate synthase (FPPs) (4). Using FPP and IPP as substrates, C 40 octaprenyl pyrophosphate (OPP) is synthesized by octaprenyl pyrophosphate synthase (OPPs) via five IPP condensation reactions with FPP (5, 6). This polymer serves as the side chain of bacterial ubiquinone or menaquinone, a component involved in electron transfer for oxidative phosphorylation (7). Previously we have identified an OPPs from hyperthermophilic bacterium Thermotoga maritima (8). Compared with its mesophilic counterpart OPPs in Escherichia coli (9), the thermophilic enzymes shows higher product specificity, higher thermal stability, and lower structural flexibility.During each IPP condensation, a new double bond is formed. Thus the prenyltransferases are classified as cis-and transtype depending on the stereoisomer of the double bond formed (10). Two DDXXD motifs in the amino acid sequences were found in trans-type prenyltransferases. The first motif is responsible for binding with FPP, and the second motif is responsible for IPP binding (11)(12)(13)(14). OPPs is a trans-type enzyme synthesizing the C 40 long chain pro...

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Crystal Structure of Recombinant Farnesyl Diphosphate Synthase at 2.6-.ANG. Resolution

Cited by 417 publications

References 21 publications

Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event

Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event

Biosynthesis of plant‐derived flavor compounds

Crystal Structure of Octaprenyl Pyrophosphate Synthase from Hyperthermophilic Thermotoga maritima and Mechanism of Product Chain Length Determination

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