Phospholipids crystal structure

Therraodjmamics of phospholipids depend on their molecular structure the conformation and the geometry of the phospholipids polar head, the orientation of the molecular backbone (glycerol in the case of glycerophospholipids) and the acyl-chaiiis orientation. NMR spectroscopy has been used extensively in order to reveal the lipid orientation in membrane structures [20]. NMR experiments have shown that except for phospatidic acid, in all phospholipid crystal structures a part of the sn-2 fatty acyl chain is parallel to the bilaycr surface. In egg phosphatidylcholines for example the averege size of the sn-2 acyl chain is 18 carbons while the sn- fatty acid is 16 carbons long. The final configuration of the two fatty acyl chains extends to the same depth from the bilayer surface and a thermodynamicaly stable conformation of the acyl lipid chains is formed [21]. 

Hauser, H., Pascher, I., and Sundell, S., 1980, Conformation of phospholipids. Crystal structure of lysophosphatidylcholine analogue, J. Mol. Biol., 137 249. 

Fig. 13. Lyotropic liquid crystal structures (a) micelle formed by a typical soap (b) vesicle formed by a typical phospholipid.

Beamer LJ, Carroll SF, Eisenberg D (1997) Crystal structure of human BPI and two bound phospholipids at 2.4 angstrom resolution. Science 276 1861—1864... 

P—S bond is elongated to 196.5 pm and the P—0(H) bond shortened to 148 pm.164 The structures of the m-vinyl carbonate (136)165 and the cyclic phosphonic anhydride (96)123 have been determined, and for the latter compound the ring was found to be almost planar. A -Ray diffraction data of deoxyuridine phosphate,166 phospholipid multilayers,167 nucleotides,168 and skeletal muscle169 have been analysed. The crystal structure of the phosphazene (137) has been established.170... 

PH domains bind phosphatidyl inositol derivatives and, due to this property, are able to mediate membrane association of signal proteins. The PH domain of PL-C61 binds to phospholipids such as Ptd(Ins)P2 with high affinity and specificity. The crystal structure of the PH domain of PL-C81 with bound Ptd(Ins)P2 surprisingly has a very similar folding topology to the PTB domain that specifically binds phosphotyrosine-containing peptides (see 8.2.3 review Lemmon et al, 1996). The importance of this similarity is not understood. 

Phospholipase C (PTC, EC 3.1.4.3) catalyzes the hydrolysis of the phosphodiester bond in phospholipids. It releases the second messenger molecule diacylglycerin (DAG) important in the signal transduction cascade and a phosphorylated headgroup . The active site of the enzyme contains three Zn ions with two of them in close proximity. Only few crystal structures are solved until now " . ... 

Franzot, G., Sjoblom, B., Gautel, M., and Djinovic Carugo, K. (2005). The crystal structure of the actin binding domain from alpha-actinin in its closed conformation Structural insight into phospholipid regulation of alpha-actinin. /. Mol. Biol. 348, 151-165. 

Fig. 4.7 Location of amlo-dipine within the membrane bilayer derived from its cen-ter-of-mass location and crystal structure. Its location near the hydrocarbon corewater interface can facilitate both a hydrophobic interaction with the phospholipid acyl chain and an ionic interaction between the protonat-ed amino function of the drug and the charged anionic oxygen of the phosphate head group. Nimodipine structure and location are consistent with only hydrophobic interactions with the phospholipid acyl chains. No electrostatic interaction with the head groups of PI was noted. (Reprinted from Fig. 2 of ref. 95 with permission from the American Chemical Society.)...

Conformations based on the few available X-ray structures of phospholipids in the crystalline state, generated from energy minimization or from conformational libraries of phospholipid alkyl chains, have been used as starting structures for the simulation. It has been argued that the latter is preferable in order to save time necessary for equilibration when starting from all-trans conformations of the alkyl chains observed in X-ray structures. To build up the configuration of the system, e.g. the lateral positions of the phospholipids, either crystal structure data or programs... 

Perisic, O., Fong, S., Lynch, D.E., Bycroft, M., and Williams, R.L., 1998, Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2. J. Biol. Chem. 273 1596-1604. 

In the bacterial PI-PLC structures, the top of the barrel rim has several hydrophobic residues that are fully exposed to solvent and poorly defined in the crystal structures (implying significant mobility). The active site of PI-PLC is accessible and well-hydrated, and these mobile elements at the top of the barrel offer a different motif for interactions of the protein with phospholipid interfaces. The PI-PLC from B. thuringiensis (nearly identical in sequence to the enzyme from B. cereus whose crystal structure was determined) exhibits the property of interfacial activation, where enhanced activity is observed when the substrate PI is present in an interface compared to monomeric substrate (Lewis et al., 1993). However, other non-substrate lipids such as phosphatidylcholine (PC), phosphatidic acid (PA), and other anionic lipids have an effect on the activity of PI-PLC toward both substrates PI and water-soluble cIP (Zhou et al., 1997). In particular, the presence of PC enhances the catalytic activity of... 

Li Y, et al. Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1. Mol. CeU, 2005 17 491-502. Wang W, et al. The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1. Proc. Natl. Acad. Sci. U.S.A, 2005 102 7505-7510. 

Figure 7.11 Crystal structure of sodium 2,3-dimyristoyl-D-glycero-l-phosphate. An e.xample of a chiral phospholipid with the typical bends of the ester groups at 0-1 and 0-3. ...

The annexins bind to phospholipids in a reversible Ca2+-dependent manner. They are implicated in membrane fusion, vesicular trafficking, and ion-channel formation. X-ray crystal structures of various soluble annexins all reveal a common backbone fold in which each of four repeats in the core domain contains five a-helices connected by short loops (Fig. 9.6a). Two of these loops come together to form Ca2+-binding sites that coordinate with the negatively charged head-group of phosphatidylserine on the cytosolic surface of membranes. Unfortunately, this association does not explain its ion-channel activity. That... 

Agonists - The existence of two receptor populations for histamine raises the interesting question of whether the chemical mechanism of histamine interaction differs between the two receptor types. Some indications of the chemical properties which may differentiate receptor action come from studies of histamine chemistry and from structure-activity considerations of congeners. Histamine in aqueous solution is a mixture of equilibrating species, viz. ionic forms, tautomers and conformers nmr studies confirm earlier pK work indicating a N -H N -H (structures 1 and 2) tautomer ratio of approximately 4 1 for histamine monocation, and a comparable ratio for histamine base. The latter result contrasts with crystal structure data and molecular orbital predictions, and may indicate an influence of solvent on tautomer stability. Recent studies of properties pertinent to consideration of ligand-receptor interactions are conformation (MO calculations and infra-red comparison of solid state and chloroform solutions of histamine base ), electronic charge distribution, metal complexation, and phospholipid inter-... 

Phospholipases are very versatile enzymes which allow the transformation of inexpensive natural products into highly valuable compounds like specific structurally defined phospholipids, organic monophosphates or diphosphates and DAG with the natural absolute configuration. Of particular synthetic utility is PLD from bacterial sources which is able to effect the phosphoryl transfer in a water-containing biphasic system. PLD shows a wide substrate specificity for both the polar head and the alcohol acceptors as well as for the lipophilic part of the molecule. The enzyme behaves like a generic phosphodiesterase with broad substrate specificity and high transphosphatidylation ability. The molecular basis of this behavior should become clear by inspection of the three-dimensional structure and comparison with other phosphoric acid ester hydrolytic enzymes. The crystal structure of this enzyme has not been elucidated. The potential of the many different PLD from plants which show peculiar substrate specificity should allow one to expand the synthetic utility to the hydrolysis-synthesis of natural and unnatural phosphatidylinositols. 

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