Protein receptors, function

B and W J Howe 1991. Computer Design of Bioactive Molecules - A Method for Receptor-Based Novo Ligand Design. Proteins Structure, Function and Genetics 11 314-328. i H L 1965. The Generation of a Unique Machine Description for Chemical Structures - A hnique Developed at Chemical Abstracts Service. Journal of Chemical Documentation 5 107-113. J 1995. Computer-aided Estimation of Symthetic Accessibility. PhD thesis. University of Leeds, itan R, N Bauman, J S Dixon and R Venkataraghavan 1987. Topological Torsion A New )lecular Descriptor for SAR Applications. Comparison with Other Descriptors. Journal of emical Information and Computer Science 27 82-85. 

FIGURE 1.4 Increasing levels of protein structure. A protein has a given amino acid sequence to make peptide chains. These adopt a 3D structure according to the free energy of the system. Receptor function can change with changes in tertiary or quaternary structure. 

Semaphorins are secreted, membrane-associated or transmembrane proteins defined by the presence of a sema-phorin protein domain (Serna domain). In the mammalian system, more than 20 semaphorins have been identified which play important roles in a variety of tissues. The best characterized receptors for mediating semaphoiin effects are members of the neuropilin and plexin families of transmembrane proteins. Semaphoiin functions are best described in the regulation of neural development, angiogenesis, immunoregulation and cancer. 

Franci C, Gosling J, Tsou CL, Coughlin SR, Charo IF (1996) Phosphorylation by a G protein-coupled kinase inhibits signaling and promotes internalization of the monocyte chemoattractant protein-1 receptor. Critical role of carboxyl-tail serines/threonines in receptor function. J Immunol 157 5606-5612... 

Fig. 3.4 Three models for prospective function(s) for OBPs during perireceptor delivery of a signal molecule odourant <=> protein <=> receptor site interactions could involve multiple roles. Ligand , OBP , combination(s) buffer and/or carrier and/or transducer from Pelosi, 1994).

Additional genes and protein receptors are believed to be important in colorectal tumorigenesis. Cyclooxygenase 2 (COX-2), which is induced in colorectal cancer cells, influences apoptosis and other cellular functions in colon cells, and overexpression of the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein involved... 

In principle, these features can be built into models of receptor activation, although the large number of disposable parameters makes testing difficult. Some of the rate and equilibrium constants must be known beforehand. One experimental tactic is to alter the relative proportions of receptors and G-protein and then determine whether the efficacy of agonists changes in the way expected from the model. The discovery that some receptors are constitutively active has provided another new approach as well as additional information about receptor function, as we shall now see. 

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