Molecule--receptor specificity.

The specificity of binding between small molecules and macromolecular receptors may be studied by comparing theoretically calculated conformational potential energy surfaces of a series of chemically similar molecules which have a range of receptor binding energies and biological activities. In this way essential requirements for binding may be highlighted, including the necessity of the small molecule adopting, or passing through, conformations which are not at energy minima and not found either in the solid state or in aqueous solution. In particular the conformational demands of the adrenergic beta-receptor and histamine H1 receptor are considered.     

Degeneracy of antibody specificity

Evidence was obtained, by direct binding assays (radioimmunoassays) and by inhibition of binding assays, that after immunization some of the antibody molecules produced are degenerate in that they bind not only the immunizing antigen, but also unrelated ligands. It can be concluded that the exquisite specificity of the immune response is not necessarily a property of any given antibody molecule but is, at least to some extent, due to the summation of specificities held in common by the population of antibody molecules produced during the response.     

Heparan sulfate-protein binding specificity

Heparan sulfate (HS) represents a large class of linear polysaccharides that are required for the function of all mammalian physiological systems. HS is characterized by a repeating disaccharide backbone that is subject to a wide range of modifications, making this class of macromolecules arguably the most information dense in all of biology. The majority of HS functions are associated with the ability to bind and regulate a wide range of proteins. Indeed, recent years have seen an explosion in the discovery of new activities for HS where it is now recognized that this class of glycans functions as co-receptors for growth factors and cytokines, modulates cellular uptake of lipoproteins, regulates protease activity, is critical to amyloid plaque formation, is used by opportunistic pathogens to enter cells, and may even participate in epigenetic regulation. This review will discuss the current state of understanding regarding the specificity of HS-protein binding and will describe the concept that protein binding to HS depends on the overall organization of domains within HS rather than fine structure.     

Species specificity of streptokinase

Streptokinase, a bacterial protein, forms a complex with human plasminogen which results in a conformational change in the plasminogen molecule and the exposure of an active center. The plasminogen-streptokinase complex is an activator of plasminogen and is rapidly converted to a plasmin-streptokinase complex which, in the human, is also an activator of plasminogen. Species differences have been found in the reaction of streptokinase with plasminogen varying from no active complex formation at one extreme to the rapid formation of an active activator complex at the other, with resultant differences in rates of complex formation and the yield of plasmin. Explanation of these species differences at a molecular level are discussed as well as the possible application of complex formation in a variety of biological systems as a mechanism to produce variation in enzyme activities in proportion to the concentration of substrate available.     

Substrate specificity of chlorophyllase

Apparent Km and V_max values were obtained for hydrolysis of methyl and ethyl chlorophyllides a, methyl and ethyl pheophorbide a, and 9-hydroxymethyl pheophorbide a by chlorophyllase from Ailanthus altissima. Analysis of substrate specificity data for chlorophyllase indicates that the presence of a 9-keto group and a methyl alcohol group esterified at the 7-position in chlorophyll derivatives results in maximum binding affinity for substrates. Data on maximum reaction rates indicate that the rate-controlling step of hydrolysis occurs after release of the alcohol from the ester. Probable high affinity chlorophyllase inhibitors can be predicted on the basis of these specificity studies.     

Species specificity of informatin

Informatin, the protein moiety of nuclear pre-mRNA containing particles, exhibits species specific antigenic properties but shows also some interspecies cross-reactivitiesat Moscowat Nijmegen     

Tissue specificity of chordin

Chordin is a tissue-specific protein antigen of notochord. Earlier this protein was discovered in the notochords of sturgeon (Acipenseridae) species; the notochord-specific antigenic determinants were detected in the notochord residues of teleost fish species and in notochord derivatives (nuclei pulposi) of mammals. Using the RIA technique, extracts from 35 samples of normal, fetal and tumour tissues of man were screened for chordin. Among other tissue samples tested, extracts from fetal brain and rectal adenocarcinoma exhibited marked cross-reactivity towards antibodies against chordin. Cross-reactivity towards chordin was observed in rabbit brain extract. This extract contained an antigen which was immunologically related (but not fully identical) to chordin. In total, in this and previous studies, 58 samples of fish and mammalian tissues were analyzed for chordin. However, antigenic determinants of chordin were identified only in extracts prepared from the notochords and nuclei pulposi as well as from brain and rectal adenocarcinoma. These findings suggest that chordin is an antigen with a restricted tissue specificity.