Phosphorylcholine structure

Segal, D.M., et al. The three-dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen-binding site. Proc. Natl. Acad. Sci. USA 71 4298-4302, 1974. 

Haslam, S.M., Houston, KM., Harnett, W., Reason, A.J., Morris, H.R. and Dell, A. (1999) Structural studies of phosphorylcholine-substituted A-glycans of filarial parasites conservation amongst species and discovery of novel chito-oligomers. Journal of Biological Chemistry 274, 20953-20960. 

Fig. 19.1. Structure of phosphorylcholine (PC). PC is involved in phosphodiester linkage to carbohydrate in a number of lower organisms, including filarial nematodes (linking sugar appears to be A/-acetylglucosamine on species examined to date).

Fig. 1 Chemical structure of water-soluble poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid (PMBV)...

The nature of the reaction catalyzed by PLC i( in which phosphatidylcholine is split into diacylglycerol and phosphorylcholine (Fig. 11) requires two proton transfer steps The first is the deprotonation of an active site water to generate the attacking hydroxide nucleophile, and the second is the protonation of the alkoxide leaving group. Although analyses of the X-ray structures of PLCSc and... 

We have recently evaluated the ATRP of a wide range of hydrophilic monomers such as 2-sulfatoethyl methacrylate (SEM), sodium 4-vinylbenzoate (NaVBA), sodium methacrylate (NaMAA), 2-(dimethylamino)ethyl methacrylate (DMA), 2-(iV-morpholino)ethyl methacrylate (MEMA), 2-(diethylamino)ethyl methacrylate (DEA), oligo(ethylene glycol) methacrylate (OEGMA), 2-hydroxyethyl methacrylate (HEMA), glycerol monomethacrylate (GMA), 2-methacryl-oyloxyethyl phosphorylcholine (MPC), and a carboxybetaine-based methacrylate [CBMA]. Their chemical structures and literature references (which contain appropriate experimental details) are summarised in Table 1. 

Another example that I now recall of poor fit between shape of a binding site and that of ligand is the immunoglobulin, or Bence-Jones protein, that binds the hapten phosphorylcholine. The X-ray structure of the antibody has been worked out and it is evident that the binding area is much larger than that of the hapten, and hardly complementary in shape. 

Structural components and function of sphingomyelin The alcohol sphingosine attached to a long-chain fatty acid produces a ceramide. Addition of a phosphorylcholine produces the phospholipid sphingomyelin, which is the only significant sphingophospholipid in humans. It is an important constituent of myelin. 

According to Mechanism 1, the ion-dipole interaction proposed by Shah and Schulman (II), Ca++ binds to the oxygen of a polarized P-O bond in the structure of the phosphorylcholine zwitterion. In spite of the speculative claims of Shah and Schulman (II) and the theoretical affirmations of Gillespie (20), this mechanism must be rejected on the basis of the theoretical arguments presented here and elsewhere (2,5,6). In brief, if such a bond existed (and the evidence (IR or NMR) is not available), it should not bear any direct relation to AV and surface dipole moments, which are generated only by ionized species and not by silent ion pairs nor by partial charges of polarized covalent bonds (2,5). 

The binding of phosphorylcholine does not significantly change the structure of the antibody, yet induced fit plays a role in the formation of many antibody-antigen complexes. A malleable binding site can accommodate many more kinds of ligands than can a rigid one. Thus, induced fit increases the repertoire of antibody specificities. 

Figure 33.11. Binding of a Small Antigen. The structure of a complex between an Fj j, fragment of an antibody and its target in this case, phosphoryl-choline. Residues from the antibody interact with phosphorylcholine through...

The challenge of how to represent the receptor that is deduced from these results is greatly helped by the use of computer graphics systems. For example, it was used to show the complementarity of molecular surfaces in the crystal structure of the complex between an antibody and lysozyme. The contact area is about 20x20 A. Side chains from one, such as Gin 121 of lysozyme, fit in a depression on the surface of the other protein. Interactions with small antigens, such as phosphorylcholine, have also demonstrated the specificity of the interactions between antibodies and antigens. 

Figure 11 Facing page) (a) Structural formula of pH-responsive triblock copol3uner consisting of poly[(diisopropylamino)ethyl methaciylate]-6-pol3Kmethacryloyloxyethyl phosphorylcholine)-6-poly[(diisopropylammo)ethyl methacrylate] prepared by ATRP technique, (b) Formation of macroscopic gels of concentrated solution of triblock copolymer, (c) Drug release behavior from triblock copolymer gels at 37°C and at pH 7.4. (From Ref. 72.)...

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