Ligand-receptor complex

The abundance of crystallographic information on the 3D structure of protein kinases, including knowledge of receptor-ligand complexes, has seen protein kinases feature consistently in datasets employed to both develop and evaluate methods for receptor-based screening. Indeed, the vast majority of literature surrounding protein kinases and receptor-based in silico... 

Molecular modelling of opioid receptor-ligand complexes, 40 (2002) 107 Molecularly imprinted polymers,... 

Several problems limit the interpretation of sTNF-R and IL-lra levels, including the specificity of currently available assays for free receptor or receptor-ligand complexes (El3). In addition, acute or chronic organ dysfunction may significantly alter the clearance of both sTNF-R and IL-lra, and the potential impact of established immunological dysfunction upon their production has not been clarified. 

Uptake of protein by hepatocytes can occur via one of two mechanisms (a) receptor-mediated en-docytosis or (b) non-selective pinocytosis, again with subsequent protein proteolysis. Similarly, a proportion of some proteins are likely degraded within the target tissue, as binding to their functional cell surface receptors triggers endocytotic internalization of the receptor ligand complex (Figure 4.7). 

Figure I. Calculated vs. observed free energies of binding for the 18 receptor-ligand complexes used to derived the LIE model in Ref. 26.

Fig. 3.1 Steps involved in drug discovery approach - a typical example. Joint efforts of classical genomics, proteomics, homology modelling, receptor- or structure-based screening approaches, and finally the structural biology efforts to determine the 3D structures of target reeeptor and receptor-ligand complex to get structural insight info their interactions...

Since adequate washing cannot realistically be obtained in less than about 50 msec, the complex half-life must be at least 250 msec (k i < 2.8 s ) for reasonable binding measurements to be obtained. Uirfortunately, the dissociation rates of many important receptor-ligand complexes are faster than this and these are not amenable to measurement by these techniques. To study the equilibrium binding of [ Hjmuscimol, we routinely use a filtration (wash) time of 0.5 sec and a wash volume of 2 ml. 

The rate of formation of a receptor-ligand complex depends on the concentration of the two species, the affinity of the complex and the nature of the underlying mechanism. As a first approximation, if one... 

Clathrin-mediated endocytosis involves the internalization of transmembrane receptor-ligand complexes stimulating the formation of a coated pit that eventually buds off the membrane to form an intracellular endocy-totic vesicle. This process is dependent on the protein clathrin that is recruited to the membrane and forms a cage-like structure around the forming pit. Internalization via clathrin-dependent pathway allows the uptake of particles approximately 120nm in size (63-65). Once internalized, the clathrin coating disassociates from the endosome to be recycled and to allow the endosome to fuse with an intracellular compartment, usually a... 

Other receptors are soluble proteins that exist in the cell cytoplasm. When complexed with their signaling molecules or ligands, they migrate to the nucleus where the receptor ligand complex binds specifically to sites on the nuclear DNA and controls protein synthesis. 

The protein-ligand binding affinity is usually expressed as the equilibrium dissociation constant, K, which is described by the following relationship between the concentrations of free receptor [ ], free ligand [S], and the receptor-ligand complex [ES ... 

ALIS measures the MS response of the ligand following its dissociation from the protein-ligand complex. Therefore, the magnitude of the MS response corresponds to the equilibrium concentration of the receptor-ligand complex concentration [ S] times the compound s MS calibration factor Cms, which depends on the ionization efficiency and other molecular properties of the ligand ... 

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