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Chembiochem : a European Journal of... Jul 2015ZG16p is a soluble mammalian lectin that interacts with mannose and heparan sulfate. Here we describe detailed analysis of the interaction of human ZG16p with...
ZG16p is a soluble mammalian lectin that interacts with mannose and heparan sulfate. Here we describe detailed analysis of the interaction of human ZG16p with mycobacterial phosphatidylinositol mannosides (PIMs) by glycan microarray and NMR. Pathogen-related glycan microarray analysis identified phosphatidylinositol mono- and di-mannosides (PIM1 and PIM2) as novel ligand candidates of ZG16p. Saturation transfer difference (STD) NMR and transferred NOE experiments with chemically synthesized PIM glycans indicate that PIMs preferentially interact with ZG16p by using the mannose residues. The binding site of PIM was identified by chemical-shift perturbation experiments with uniformly (15)N-labeled ZG16p. NMR results with docking simulations suggest a binding mode of ZG16p and PIM glycan; this will help to elucidate the physiological role of ZG16p.
Topics: Carbohydrate Sequence; Host-Pathogen Interactions; Humans; Lectins; Molecular Docking Simulation; Molecular Sequence Data; Mycobacterium; Mycobacterium Infections; Phosphatidylinositols; Protein Binding
PubMed: 25919894
DOI: 10.1002/cbic.201500103 -
Biochimica Et Biophysica Acta Feb 1990Non-hydrolysable analogues of phosphatidylinositol were synthesized and tested as inhibitors of phosphatidylinositol-specific phospholipase C from Bacillus cereus. In...
Non-hydrolysable analogues of phosphatidylinositol were synthesized and tested as inhibitors of phosphatidylinositol-specific phospholipase C from Bacillus cereus. In these molecules, the phosphodiester bond of phosphatidylinositol hydrolyzed by the phospholipase was replaced by a phosphonate linkage and a simpler hydrophobic group replaced the diacylglycerol moiety. One of the phosphonates also contained a carboxylate functional group suitable for matrix attachment. All three synthetic phosphonates inhibited the phospholipase C activity in a concentration-dependent manner, with the analogue most closely resembling the structure of the natural substrate, phosphatidylinositol, being the most potent inhibitor. The data indicate that phosphonate analogues of phosphatidylinositol may be useful for study of phospholipase C and other proteins interacting with myo-inositol phospholipids.
Topics: Bacillus cereus; Models, Molecular; Organophosphonates; Phosphatidylinositols; Type C Phospholipases
PubMed: 2106349
DOI: 10.1016/0005-2760(90)90172-t -
Critical Reviews in Biochemistry and... 2014Phosphatidylinositol lipids are signaling molecules involved in nearly all aspects of cellular regulation. Production of phosphatidylinositol 4-phosphate (PI4P) has long... (Review)
Review
Phosphatidylinositol lipids are signaling molecules involved in nearly all aspects of cellular regulation. Production of phosphatidylinositol 4-phosphate (PI4P) has long been recognized as one of the first steps in generating poly-phosphatidylinositol phosphates involved in actin organization, cell migration, and signal transduction. In addition, progress over the last decade has brought to light independent roles for PI4P in membrane trafficking and lipid homeostasis. Here, we describe recent advances that reveal the breadth of processes regulated by PI4P, the spectrum of PI4P effectors, and the mechanisms of spatiotemporal control that coordinate crosstalk between PI4P and cellular signaling pathways.
Topics: 1-Phosphatidylinositol 4-Kinase; Animals; Humans; Phosphatidylinositol Phosphates; Phosphatidylinositols; Signal Transduction
PubMed: 24219382
DOI: 10.3109/10409238.2013.853024 -
Nature Jan 1993
Topics: Carbon Radioisotopes; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Phosphatidylserines; Protein Binding; Vinculin
PubMed: 8380904
DOI: 10.1038/361214b0 -
Current Opinion in Cell Biology Apr 2001The reversible localization of signaling proteins to both the plasma and the internal membranes of cells is critical for the selective activation of downstream functions... (Review)
Review
The reversible localization of signaling proteins to both the plasma and the internal membranes of cells is critical for the selective activation of downstream functions and depends on interactions with both proteins and membrane lipids. New structural and biochemical analyses of C1, C2, PH, FYVE, FERM and other domains have led to an unprecedented amount of information on the molecular interactions of these signaling proteins with regulatory lipids. A wave of studies using GFP-tagged membrane binding domains as reporters has led to new quantitative insights into the kinetics of these signaling mechanisms.
Topics: Animals; Biological Transport; Cell Membrane; Humans; Membrane Lipids; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Protein Binding; Protein Structure, Tertiary; Proteins
PubMed: 11248547
DOI: 10.1016/s0955-0674(00)00191-5 -
The Journal of Biological Chemistry Dec 1989The metabolism of polyphosphoinositides has been shown to be an important factor in controlling the proliferation of Saccharomyces cerevisiae. The monophosphate form of...
The metabolism of polyphosphoinositides has been shown to be an important factor in controlling the proliferation of Saccharomyces cerevisiae. The monophosphate form of phosphatidylinositol has been assumed to be phosphatidylinositol 4-phosphate (PI-4-P). Recent evidence from our laboratory has established that a phosphatidylinositol (PI) kinase, which phosphorylates the D-3 position of the inositol ring (PI 3-kinase), is associated with many activated protein-tyrosine kinases and may play an important role in the signaling of cell proliferation (Auger, K. R., Serunian, L. A., Soltoff, S. P., Libby, P., and Cantley, L. C. (1989) Cell 57, 167-175). To determine the evolutionary conservation of this enzymatic activity, we investigated its presence in yeast. In vitro PI kinase assays of yeast cell homogenates demonstrated that PI 3-kinase activity was present. Preliminary biochemical characterization of the activity suggested that it was quite different from the mammalian enzyme yet catalyzed the same reaction, i.e. phosphorylating the D-3 hydroxyl position of the inositol ring of phosphatidyl-myo-inositol. [3H]Inositol labeling of intact yeast cells with the subsequent extraction, deacylation, and high performance liquid chromatography analysis of the lipids demonstrated that PI-3-P was as abundant as the PI-4-P isomer. The conservation of the enzymatic activity from yeast to man suggests that it has an important functional role in the cell cycle.
Topics: Inositol; Phosphatidylinositol 3-Kinases; Phosphatidylinositol Phosphates; Phosphatidylinositols; Phosphotransferases; Saccharomyces cerevisiae
PubMed: 2555343
DOI: No ID Found -
International Journal of Molecular... Jun 2019Polyphosphoinositides (PPIns) are a family of seven lipid messengers that regulate a vast array of signalling pathways to control cell proliferation, migration, survival... (Review)
Review
Polyphosphoinositides (PPIns) are a family of seven lipid messengers that regulate a vast array of signalling pathways to control cell proliferation, migration, survival and differentiation. PPIns are differentially present in various sub-cellular compartments and, through the recruitment and regulation of specific proteins, are key regulators of compartment identity and function. Phosphoinositides and the enzymes that synthesise and degrade them are also present in the nuclear membrane and in nuclear membraneless compartments such as nuclear speckles. Here we discuss how PPIns in the nucleus are modulated in response to external cues and how they function to control downstream signalling. Finally we suggest a role for nuclear PPIns in liquid phase separations that are involved in the formation of membraneless compartments within the nucleus.
Topics: Animals; Cell Nucleus; Chemical Phenomena; Computational Biology; Humans; Intranuclear Space; Lipid Metabolism; Metabolic Networks and Pathways; Nuclear Envelope; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Signal Transduction
PubMed: 31248120
DOI: 10.3390/ijms20122991 -
Biochemical Society Symposium 2007Interconversions of phosphoinositides play a pivotal role during phagocytosis and at the subsequent stages of phagosomal maturation into the phagolysosome. Several model... (Review)
Review
Interconversions of phosphoinositides play a pivotal role during phagocytosis and at the subsequent stages of phagosomal maturation into the phagolysosome. Several model systems have been used to study the role of phosphoinositides in phagosomal membrane remodelling. These include phagosomes formed by inanimate objects such as latex beads, or pathogenic bacteria, e.g. Mycobacterium tuberculosis. The latter category provides naturally occurring tools to dissect membrane trafficking processes governing phagolysosome biogenesis. M. tuberculosis persists in infected macrophages by blocking Rab conversion and affecting Rab effectors. One of the major Rab effectors involved in this process is the type III phosphatidylinositol 3-kinase hVPS34. The lipid kinase hVPS34 and its enzymatic product PtdIns3P are critical for the default pathway of phagosomal maturation into phagolysosomes. Mycobacteria block PtdIns3P production and thus arrest phagosomal maturation. PtdIns3P is also critical for the process of autophagy, recently recognized as an effector of innate immunity defenses. Induction of autophagy by pharmacological, physiological, or immunological means, overcomes mycobacterial phagosome maturation block in a PtdIns3P generation dependent manner and eliminates intracellular M. tuberculosis. PtdIns3P and PtdIns3P-dependent processes represent an important cellular nexus where fundamental trafficking processes, disease causing host-pathogen interactions, and innate and adaptive immunity defense mechanisms meet.
Topics: Animals; Autophagy; Humans; Models, Biological; Mycobacterium tuberculosis; Phagocytosis; Phagosomes; Phosphatidylinositol Phosphates; Phosphatidylinositols
PubMed: 17233587
DOI: 10.1042/BSS0740141 -
The Journal of Biological Chemistry Dec 1990Three polyphosphoinositides containing phosphate at the D-3 position of the inositol ring can be generated in vitro by phosphorylation of phosphatidylinositol,...
A novel pathway for the formation of phosphatidylinositol 3,4-bisphosphate. Phosphorylation of phosphatidylinositol 3-monophosphate by phosphatidylinositol-3-monophosphate 4-kinase.
Three polyphosphoinositides containing phosphate at the D-3 position of the inositol ring can be generated in vitro by phosphorylation of phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate by a phosphatidylinositol-3-kinase (Auger, K. R., Serunian L. A., Soltoff, S. P., Libby, P., and Cantley, L. C. (1989) Cell 57, 167-175. An alternative pathway for in vivo synthesis of one of these lipids was recently suggested: phosphatidylinositol 3,4-bisphosphate could be produced by phosphorylation of phosphatidylinositol 3-phosphate at the D-4 position of the inositol ring (Yamamoto, K., and Lapetina, E. G. (1990) Biochem. Biophys. Res. Commun. 168, 466-472). Here we demonstrate the presence of an enzyme in human platelets that phosphorylates [32P]phosphatidylinositol 3-phosphate to produce [32P]phosphatidylinositol 3,4-bisphosphate. This enzyme is Mg2(+)-dependent and its apparent molecular mass is approximately 150 kDa as estimated by sucrose gradient centrifugation and gel filtration chromatography. Unlike the major phosphatidylinositol-4-kinase in platelets that is stimulated by the detergent Nonidet P-40, the phosphatidylinositol-3-phosphate-4-kinase is inhibited by Nonidet P-40. Both activities are also differentiated by the action of adenosine. The discovery of this new enzyme raises the possibility that multiple pathways exists for generating D-3 phosphorylated phosphoinositides.
Topics: 1-Phosphatidylinositol 4-Kinase; Adenosine; Blood Platelets; Cell Line; Centrifugation, Zonal; Chromatography, High Pressure Liquid; Cytosol; Humans; Kinetics; Leukemia, Erythroblastic, Acute; Phosphatidylinositol 3-Kinases; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols; Phospholipids; Phosphorus Radioisotopes; Phosphorylation; Phosphotransferases
PubMed: 2176203
DOI: No ID Found -
Biochemical Society Transactions Aug 1999
Topics: 3T3 Cells; Animals; Antibodies; Antibody Formation; Cell Line; Cell Nucleus; Chromatography, Thin Layer; Dose-Response Relationship, Immunologic; Humans; Immunoblotting; Immunologic Techniques; Interphase; Luminescent Measurements; Mice; Mice, Inbred BALB C; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols
PubMed: 10917659
DOI: 10.1042/bst0270648