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Showing 1 to 20 of 91 for “"Isoprenoid"”.
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Targeting isoprenoid biosynthesis for drug discovery
… resistance, there is a need for new drugs, and isoprenoid biosynthesis is an attractive target for drug discovery. In chapter 1, I briefly introduce the isoprenoid biosynthesis pathway and two important drug targets: a trans-prenyl transferase farnesyl diphosphate synthase (FPPS), and a …
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Engineering a novel pathway for isoprenoid synthesis
Isoprenoids comprise a large class of chemicals, of significant interest due to their diverse properties. Most isoprenoids are plant secondary metabolites and are of commercial importance due to their varied applications in fields spanning medicine, agriculture, flavors, fragrances, cosmetics and …
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Targeting isoprenoid and quinone biosynthesis for antimicrobial discovery
"Enzymes in isoprenoid biosynthesis pathway play important roles in all living organisms. Here we report the first structure of heptaprenyl diphosphate synthase from Staphylococcus aureus (SaHepPPS) together with an investigation of its mechanism of action, and inhibition. HepPPS is involved in …
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Mechanism, inhibition and spectroscopy of isoprenoid biosynthesis enzymes
Isoprenoids (or terpenes) are a large class of compounds with great physiological importance in all kingdoms of life. The research in this work explored the mechanism and inhibition of several enzymes in two important pathways for isoprenoid biosynthesis. The first pair of enzyme are IspG and IspH, …
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SYNTHETIC AND BIODEGRADATION STUDIES OF SOME SEDIMENTARY ISOPRENOID HYDROCARBONS
… other geologically-occurring 'irregular' acyclic isoprenoid alkanes is described.
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SOURCES AND STRUCTURES OF COMMONLY OCCURRING HIGHLY BRANCHED ISOPRENOID ALKENES
Highly branched isoprenoid (HBI) alkenes are ubiquitous lipids which have been identified in numerous geochemical samples, ranging from recent sediments to ancient oils. At the outset of the current investigation, the diatomaceous algae Haslea ostrearia (C25 alkenes) and Rhizosolenia setigera (C25 …
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Experimental and Computational Study of Bisphosphonates Targeting Isoprenoid Biosynthesis Pathway
Bisphosphonates are a class of drugs widely used to treat bone resorption diseases. Recently, bisphosphonates have been found to have anti-cancer, anti-parasitic, anti-bacterial and herbicidal activity. They also have the unexpected property of activating human gammadelta T cells to kill tumor …
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Isolation and Characterization of an Isoprenoid Transporter Protein in Manduca sexta
… locations to ensure proper cell function. Isoprenoids are metabolite molecules implicated in cell growth, energy production, and act as precursor to steroids, cholesterol, and other derived compounds in living organisms. Within the isoprenoid pathway, isopentenyl pyrophosphate (IPP) was …
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STRUCTURAL CHARACTERISATION OF HIGHLY BRANCHED ISOPRENOID ALKENES FROM SEDIMENTS AND ALGAE
At least fourteen C25 highly branched isoprenoid (HBI) alkenes have been previously reported in estuarine and coastal sediments from locations worldwide. The parent alkane structure has been proven but only a few of the double bond positions established previously. A wide body of evidence suggests …
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The relevance of bacterial isoprenoid biosynthetic pathways for host-microbe interactions
… to investigate the relevance of two bacterial isoprenoid biosynthetic pathways (Mevalonate (MVAL) and 2-C-methyl-D-erythritol 4-phosphate (MEP)) for host-microbe interactions. We determined a significant reduction in microbial diversity in the murine gut microbiota (by next generation …
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Structural Characterisation and the Diagenetic Pathways of C25 Highly Branched Isoprenoid Hydrocarbons
Highly branched isoprenoid (HBI) hydrocarbons have been widely reported in recent sediments. It is known that two species of diatomaceous algae, the diatoms Haslea ostrearia and Rhizosolenia setigera are able to biosynthesise C25 HBI alkenes. Large scale cultures of H. ostrearia studied previously, …
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The Dietary Isoprenoid Perillyl Alcohol Inhibits Telomerase Activity in Prostate Cancer Cells
<p>This is the first evidence that a plant-derived compound–perillyl alcohol regulates telomerase activity via the mammalian target of rapamycin (mTOR) pathway in prostate cancer cells. Telomerase–the enzyme responsible for immortalizing cells through telomeric repeats addition–is de-repressed …
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Isoprenoid Biosynthesis Pathway as a Drug Target for Bisphosphonates: Transcriptional Profile Investigation
Bisphosphonates are known as potent inhibitors of the enzyme farnesyl diphosphate synthase (FPPS) and are clinically used to treat bone related disorders such as osteoporosis and bone cancer. Here we describe the development, testing and study of the mechanism of action of novel bisphosphonates as …
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Studies and applications of protein prenylation using isoprenoid analogues and site-directed mutagenesis
The site-specific enzymatic modification of proteins offers a powerful tool both for the development of new research techniques and for the development of more effective therapeutics. Protein farnesyltransferase (PFTase) is a promising tool in the field of site-specific protein modification due to …
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Synthesis of Novel Isoprenoid Diphosphate Analogs as Chemical Tools to Investigate Protein Geranylgeranylation
… use a combinatorial approach in which we screen isoprenoid pyrophosphate analogs against a synthetic Dansyl-GCaaX peptide library (the minimal recognition sequence of PTases; Dansyl-G = Dansyl-glycine, C = Cys, a = aliphatic amino acid, X = a small subset of amino acids, which in general …
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Enzymes as Drug Targets in the Isoprenoid Biosynthesis Pathway: Structure, Mechanism and Inhibition
Enzymes in isoprenoid biosynthesis pathway play important roles in all living organisms. Several of them have been identified as drug targets. Here we reported the inhibition study of isopentenyl diphosphate/dimethylallyl diphosphate isomerase (IPPI) and deoxyzylolus reductoisomerase (DXR), along …
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Kinetic and structural studies on the first three enzymes in Bacillus anthracis isoprenoid biosynthesis.
… on the first three enzymes in Bacillus anthracis isoprenoid biosynthesis.
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Gene expression and biochemistry of isoprenoid biosynthesis in the glandular secretory trichomes of Artemisia annua
The Chinese herb Artemisia annua possesses small 10-cell biseriate glandular trichomes on the surface of its aerial tissues. These trichomes were isolated from floral tissue using a Bead Beater based method. Expression patterns of expressed sequence tags from a trichome library whose Basic Local …
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Structure, function and inhibition of GcpE, FPPS and GGPPS: targeting isoprenoid biosynthesis for drug discovery
… synthase (GGPPS) are enzymes involved in isoprenoid biosynthesis. Most bacterial IspGs contain two domains: a TIM barrel (A) and a 4Fe4S domain (B), but in plants and malaria parasites there is a large insert domain (A*) whose structure and function are unknown. We show bacterial IspGs …
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Mechanisms of action and inhibition of [4Fe-4S] proteins IspG and IspH in isoprenoid biosynthesis
… (also known as the non-mevalonate pathway) of isoprenoid biosynthesis is potentially an important anti-bacterial and anti-malarial drug target. However, the catalytic mechanisms of the last two enzymes in this pathway, IspG (also known as GcpE) and IspH (also known as LytB) were largely …
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