Ether lipids in biomembranes

Paltauf, Fritz

doi:10.1016/0009-3084(94)90054-x

Cited by 195 publications

(141 citation statements)

References 232 publications

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“…This is consistent with our results from gel filtration and the recent characterization of a Group II GGGPS from T. acidophilum (TaGGGPS) (12). The structure of AfGGGPS in the P3 1 space group confirms its dimeric nature, 5 as does the crystal structure of its PcrB homologue from B. subtilis (BsPcrB; Protein Data Bank code 1VIZ). Considering these results, it is not immediately obvious from sequence alignments ( Fig.…”

Section: Resultssupporting

confidence: 90%

“…Third, the isoprenoid chains are bound to G1P through ether, not ester, linkages. Of these traits, the glycerol phosphate stereochemistry is the most distinctive because ether-linked lipids are known to exist in some eukaryotes and bacteria (5,6), and phospholipid fatty acids have recently been described in Archaea (7). To date, however, there is no known exception to the G1P backbone stereochemistry of archaeal lipids or to the G3P backbone stereochemistry found in bacterial and eukaryotic lipids.…”

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confidence: 99%

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The Crystal Structure of (S)-3-O-Geranylgeranylglyceryl Phosphate Synthase Reveals an Ancient Fold for an Ancient Enzyme

Payandeh

Fujihashi

Gillon

et al. 2006

Journal of Biological Chemistry

101

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We report crystal structures of the citrate and sn-glycerol-1-phosphate (G1P) complexes of (S)-3-O-geranylgeranylglyceryl phosphate synthase from Archaeoglobus fulgidus (AfGGGPS) at 1.55 and 2.0 Å resolution, respectively. AfGGGPS is an enzyme that performs the committed step in archaeal lipid biosynthesis, and it presents the first triose phosphate isomerase (TIM)-barrel structure with a prenyltransferase function. Our studies provide insight into the catalytic mechanism of AfGGGPS and demonstrate how it selects for the sn-G1P isomer. The replacement of "Helix 3" by a "strand" in AfGGGPS, a novel modification to the canonical TIMbarrel fold, suggests a model of enzyme adaptation that involves a "greasy slide" and a "swinging door." We propose functions for the homologous PcrB proteins, which are conserved in a subset of pathogenic bacteria, as either prenyltransferases or being involved in lipoteichoic acid biosynthesis. Sequence and structural comparisons lead us to postulate an early evolutionary history for AfGGGPS, which may highlight its role in the emergence of Archaea.The membrane lipids found in Archaea are a defining characteristic of this domain of life (1). These lipids are based on a core architecture where branched-chain saturated hydrocarbons are connected to glycerol through ether linkages (2, 3). In hyperthermophiles, two diphytanylglyceryl units are often linked covalently through their hydrocarbon tails to form tetraether lipids that completely span the membrane. In addition, archaeal membrane lipids have three general characteristics that distinguish them from their bacterial and eukaryotic counterparts (4). First, the phospholipid backbone is built upon the opposite glycerol stereoisomer, sn-glycerol-1-phosphate (G1P), 4 not the sn-glycerol-3-phosphate (G3P) backbone found in bacteria and eukaryotes. Second, the hydrophobic chains are isoprenoid derivatives instead of fatty acids. Third, the isoprenoid chains are bound to G1P through ether, not ester, linkages. Of these traits, the glycerol phosphate stereochemistry is the most distinctive because ether-linked lipids are known to exist in some eukaryotes and bacteria (5, 6), and phospholipid fatty acids have recently been described in Archaea (7). To date, however, there is no known exception to the G1P backbone stereochemistry of archaeal lipids or to the G3P backbone stereochemistry found in bacterial and eukaryotic lipids.The biosynthesis of archaeal membrane lipids is schematically illustrated in (Fig. 1). In brief, dimethylallyl diphosphate (DMAPP) and its isomer isopentenyl diphosphate are synthesized by a mevalonate-like pathway (2, 8). Long isoprenoid chains are produced from these fivecarbon precursors by consecutive condensations through the action of a prenyl diphosphate synthase. The committed step in archaeal lipid synthesis occurs with the formation of an ether linkage between G1P and an isoprenoid diphosphate, usually geranylgeranyl diphosphate (GGPP). Separate enzymes catalyze the sequential transfer of isoprenoid units onto ...

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Section: Resultssupporting

confidence: 90%

mentioning

confidence: 99%

The Crystal Structure of (S)-3-O-Geranylgeranylglyceryl Phosphate Synthase Reveals an Ancient Fold for an Ancient Enzyme

Payandeh

Fujihashi

Gillon

et al. 2006

Journal of Biological Chemistry

101

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“…This difference was attributed to the change in the microenvironment experienced by the probe in these two cases induced by the change in interfacial chemistry of the two phospholipids. This differential dynamics observed in ester-and ether-linked lipids assumes relevance since ether-linked phospholipids are functionally important lipids found in halophilic bacteria, cardiac tissue, and the central nervous system 80 and in light of the functional significance of ether lipids in animal models. 81 Interestingly, the magnitude of REES was also found to be dependent on the charge of the membrane.…”

Section: 72mentioning

confidence: 89%

Organization and Dynamics of Membrane Probes and Proteins Utilizing the Red Edge Excitation Shift

2011

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Dynamics of confined water has interesting implications in the organization and function of molecular assemblies such as membranes. A direct consequence of this type of organization is the restriction imposed on the mobility of the constituent structural units. Interestingly, this restriction (confinement) of mobility couples the motion of solvent (water) molecules with the slow moving molecules in the assembly. It is in this context that the red edge excitation shift (REES) represents a sensitive approach to monitor the environment and dynamics around a fluorophore in such organized assemblies. A shift in the wavelength of maximum fluorescence emission toward higher wavelengths, caused by a shift in the excitation wavelength toward the red edge of the absorption band, is termed REES. REES relies on slow solvent reorientation in the excited state of a fluorophore that can be used to monitor the environment and dynamics around a fluorophore in a host assembly. In this article, we focus on the application of REES to monitor organization and dynamics of membrane probes and proteins.

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“…Ether lipids are known to be ubiquitous in the cell membranes of mammals, 16 marine organisms 17 and archaea. 18 These ether lipids, however, are 1-O-alkyl lipids, whereas the 3-O-alkyl lipids in kribellosides are rare.…”

Section: Stereochemistry Of the Kribellosidesmentioning

confidence: 99%

Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6

et al. 2017

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Yeast capping enzymes differ greatly from those of mammalian, both structurally and mechanistically. Yeast-type capping enzyme repressors are therefore candidate antifungal drugs. The 5ʹ-guanine-N7 cap structure of mRNAs are an essential feature of all eukaryotic organisms examined to date and is the first co-transcriptional modification of cellular pre-messenger RNA. Inhibitors of the RNA 5ʹ-triphosphatase in yeast are likely to show fungicidal effects against pathogenic yeast such as Candida. We discovered a new RNA 5ʹ-triphosphatase inhibitor, designated as the kribellosides, by screening metabolites from actinomycetes. Kribellosides belong to the alkyl glyceryl ethers. These novel compounds inhibit the activity of Cet1p (RNA 5ʹ-triphosphatase) from Saccharomyces cerevisiae in vitro with IC 50 s of 5-8 μM and show antifungal activity with MICs ranging from 3.12 to 100 μg ml À1 against S. cerevisiae.

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Ether lipids in biomembranes

Cited by 195 publications

References 232 publications

The Crystal Structure of (S)-3-O-Geranylgeranylglyceryl Phosphate Synthase Reveals an Ancient Fold for an Ancient Enzyme

The Crystal Structure of (S)-3-O-Geranylgeranylglyceryl Phosphate Synthase Reveals an Ancient Fold for an Ancient Enzyme

Organization and Dynamics of Membrane Probes and Proteins Utilizing the Red Edge Excitation Shift

Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6

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