Receptor-substrate binding, enzymes

The recognition in 1894 by Emil Fischer that binding must be selective, as part of the study of receptor-substrate binding by enzymes. He described this by a lock and key image of steric fit in which the... 

The quantity of any given solute being presented to the reabsorptive mechanisms is determined by the product of the GFR and the solute concentration in plasma. One of the features of any carrier-mediated process is its limited capacity. Binding of a substance to its transport protein follows the same principles as substrate binding to an enzyme or hormone binding to its receptor so we may appropriately liken the dynamics to Michaelis-Menten kinetics. 

Once autophosphorylation begins, a complex of other events ensues. An insulin receptor substrate (IRS-1) binds the receptor and is phosphorylated on tyrosine residues, allowing proteins with SH2 (src homology) domains to bind to the. phosphotyrosine residues on IRS-1 and become active. In this way, the receptor activates several enzyme cascades, which involve ... 

Fig. 8.20. Modular composition of adaptor proteins. Adaptor proteins do not show any enzyme activity of their own, but rather they contain protein modules which help to bind signal proteins into signal pathways. IRS-1 insulin receptor substrate 1 PTB phosphotyrosine binding domain PH pleckstrin homology domain P phosphotyrosine-containing binding site for SH2 or PTB domains HLH helrx-loop-hehx DNA binding motif...

G protein j3y-subunit <1, 3, 4> (<3> lOfold activation, /f-ARK 1 and 2, increases incorporation of phosphate from 4 to 10 mol phosphate/mol receptor [13] <3> activates, binding domain is localized to the C-terminal region of j3-ARK [15,17,28] <3> from brain, binds to the C-terminal half of the PH domain [17] <3> from bovine brain, -ARK 1 and 2 requirement, selectivity for Py subunits, both isoforms differentiate between defined Py subunits [24] <3> requirement, binding plays an important role in specifically targeting the enzyme complex to its receptor substrate [25] <4> from brain, stimulates the phosphorylation of rhodopsin, but not of the peptide RRREEEEESAAA,... 

The binding of small molecules to larger ones is basic to most biological phenomena. Substrates bind to enzymes and hormones bind to receptors. Metal ions bind to ATP, to other small molecules, and to metalloproteins. Hydrogen ions bind to amino acids, peptides, nucleotides, and most macromolecules. In this section we will consider ways of describing mathematically the equilibria involved. 

The Ca2+-phosphoinositide signaling pathway. Key proteins include hormone receptors (R), a G protein (G), a phosphoinositide-specific phospholipase C (PLC), protein kinase C substrates of the kinase (S), calmodulin (CaM), and calmodulin-binding enzymes (E), including kinases, phosphodiesterases, etc. (PIP2, phosphatidylinositol-4,5-bisphosphate DAG, diacylglycerol. Asterisk denotes activated state. Open arrows denote regulatory effects.)... 

Equation 5.8 bears a striking resemblance to the Michaelis-Menten equation (Equation 5.9) because both equations link a binding event (receptor-ligand or enzyme-substrate) to an outcome (response or conversion). 

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