Substrates receptors

According to these basic concepts, molecular recognition implies complementary lock-and-key type fit between molecules. The lock is the molecular receptor and the key is the substrate that is recognised and selected to give a defined receptor—substrate complex, a coordination compound or a supermolecule. Hence molecular recognition is one of the three main pillars, fixation, coordination, and recognition, that lay foundation of what is now called supramolecular chemistry (8—11). 

Information may be stored in the architecture of the receptor, in its binding sites, and in the ligand layer surrounding the bound substrate such as specified in Table 1. It is read out at the rate of formation and dissociation of the receptor—substrate complex (14). The success of this approach to molecular recognition ties in estabUshing a precise complementarity between the associating partners, ie, optimal information content of a receptor with respect to a given substrate. 

Fig. 1. Schematic representation of a receptor—substrate (host—guest) complex involving cavity inclusion of the substrate and the formation of different types of weak supramolecular interactions between receptor (hatched) and substrate (dotted).

The weak intemiolecular forces that are principally involved in stabilizing receptor-substrate interactions and involved in molecular recognition processes (16) are summarized in Table 2. Examples are shown in Figure 1. 

Fig. 2. Principle mechanisms of formation of a receptor—substrate complex (a) Fischer s rigid "lock-and-key" model (b) "induced fit" model showing...

From the kinetic point of view the facts are different and the order is reverse, ie, the rigid highly preorganized spherands are slow, as contrasted with the flexible barely preorganized podands that are fast both in formation and decomposition of the receptor—substrate (host—guest) complex (20,21). 

Topology. This parameter may have reference to either the receptor as an individual molecular stmcture or to the receptor—substrate complex on a higher level of organization that is direcdy related to the mode and efficiency of molecular recognition (14,30). 

Fig. 11) form very strong and selective complexes with Fe or actinide and lanthanide ions (63,64) while a similar receptor with hard endocarboxyhc acid groups is efficient for hard and ions showing again responsibility of a charge density effect in the receptor—substrate recognition (65). Thus,... 

Fig. 22. Principle of chiral receptor—substrate recognition (a) formation of diastereomeric inclusion complexes (b) three-point interaction model.

Fig. 24. Receptor substrate complexes involving particular substrate recognition.

However, all the receptors hitherto discussed are monomolecular species which possess a monomolecular cavity, pocket, cleft, groove or combination of it including the recognition sites to yield a molecular receptor—substrate complex. They can be assembled and preserved ia solution although there are dependences (see below). By way of contrast, molecular recognition demonstrated ia the foUowiag comes from multimolecular assembly and organization of a nonsolution phase such as polymer materials and crystals. 

The low detection limit, high sensitivity, and fast response times of chemoreceptor-based biosensors result primarily from the extremely high binding constants of the receptor R for the target substrate S. The receptor—substrate binding may be described... 

Receptor—substrate-binding constants are typically between 10 and 10, at equimolar ratios, implying that when a receptor—substrate... 

Insulin Receptor. Figure 1 Structure and function of the insulin receptor. Binding of insulin to the a-subunits (yellow) leads to activation of the intracellular tyrosine kinase ((3-subunit) by autophosphorylation. The insulin receptor substrates (IRS) bind via a phospho-tyrosine binding domain to phosphorylated tyrosine residues in the juxtamembrane domain of the (3-subunit. The receptor tyrosine kinase then phosphorylates specific tyrosine motifs (YMxM) within the IRS. These tyrosine phosphorylated motifs serve as docking sites for some adaptor proteins with SRC homology 2 (SH2) domains like the regulatory subunit of PI 3-kinase. 

The catalytic pi 10 subunit has four isoforms, all of which contain a kinase domain and a Ras interaction site. In addition, the a, (3, and y isoforms possess an interaction site for the p85 subunit. The class I enzymes can be further subdivided class IA enzymes interact through their SH2 domains with phosphotyrosines present on either protein tyrosine kinases or to docking proteins such as insulin-receptor substrates (IRSs GAB-1) or linkers for activation of T cells (LATs in the case of T cells). 

Yenush L, Fernandez R, Myers MG Jr et al 1996 The Drosophila insulin receptor activates multiple signaling pathways but requires insulin receptor substrate proteins for DNA... 

Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW and Shulman GI. 2002. Mechanism by which fatty acids inhibit insulin activation ofinsuhn receptor substrate-1 (IRS-l)-associatedphosphatidylinositol 3-kinase activity in muscle. J Biol Chem 27 277(52) 50230-50236. 

IRS insulin receptor substrate MRI magnetic resonance imaging... 

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