Ligands functional role

CJ-Receptors are localized ia the brain stem and limbic stmcture, regions associated with endocrine function (76). In the periphery, CJ-receptors are found in the Hver, heart, ileum, vas deferens, and on lymphocytes and thymocytes. Although there is insufficient evidence to clearly define the functional role of CNS CJ-sites, based on the effects of PCP and the interaction of haloperidol with CJ-sites, CJ-receptor ligands may be antipsychotics or used for the treatment of substance abuse. Several CJ-receptor ligands have shown neuroprotective effects in vivo. Ifenprodil (315) and CNS 1102 (316) are being developed for treatment of stroke (Table 18). 

As to the functional role of sFas variants, there have been several reports based on apoptosis inhibition tests (Cl, Jl, L6, PI). According to these smdies, all sFas variants observed in normal donors are able to block the apoptosis induced by either an agonistic antibody or the natural Fas ligand in Fas-positive cells. Injection of sFas into mice significantly alters lymphocyte development (C3). Although the functional machinery remains controversial, Papoff et al. (PI) have proposed an attractive hypothetical model of structure/function relationships for the Fas molecule, as shown in Fig. 5. This model appears to be supported by the fact that all sFas variants have N-terminal ends containing the activation domain of 49 amino acids, which is required for proximal Fas ligand-mediated events. 

In the absence of crystallographic or NMR data, predictive techniques based on protein primary sequences can be used to elaborate crude 3D models. Such models will suggest that certain amino acid residues are involved in forming the active (receptor) site. The assignment of structural or functional roles to particular residues can be tested by site-directed mutagenesis, and the model can be further refined by consideration of SAR among ligands. 

The contributors to this volume have shown how far our understanding of the molecular mechanisms of G protein signaling has come, but also how much remains to be discovered. What is the chemo-mechanical mechanism of G protein activation by receptors What are the relevant states of receptors how are they differentially stabilized by ligands what is the functional role of receptor dimerization in the modulation and control of G protein activation, or the coordination of other signaling functions. Do G protein signalosomes exist If so, what (in addition to the obvious ) are their components how tightly are they integrated—kinetically and structurally—and how and where are they assembled at the plasma... 

Leysen JE, Niemegeers CJ, Van Nueten JM, Laduron PM. [3H]Ketanserin (R 41 468), a selective 3H-ligand for serotonin2 receptor binding sites. Binding properties, brain distribution, and functional role. Mol Pharmacol 1982 21 301-314. 

The body of literature concerning the functional roles of delta opioid receptors in the digestive tract is somewhat complicated by the results of studies that employed opioid agonists or antagonists with relatively poor selectivity for opioid receptor types (e.g., capable of interacting with both delta and mu opioid receptors within a narrow concentration range). Such ligands include... 

FIGURE 16.1 Multivalent binding of a bacterium to the clustered carbohydrate ligand carrying matching terminal carbohydrate residue(s) found in the host cell surface. The multivalent interaction prevents the attachment of the bacterium to the host cell surface. The functional role of the linker is the optimal presentation of the glycan into the binding site of the receptor, but it may also be involved in additional hydrophobic contacts. 

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