Regulatory binding sites

It is clear from both Figs. 8.20 and 8.21 that CTP acts as an inhibitor while ATP acts as an activator. It is now established that both CTP and ATP bind to the regulatory binding site, which differs from the catalytic sites. The remarkable similarity between the equilibrium Bis on the one hand and the kinetic data on the other hand confirms the assertion made at the beginning of this chapter, that allosteric effects can be studied in equilibrated systems. 

Despite the ubiquitous nature of serine proteases, it is possible to design specific thrombin inhibitors by taking advantage of the accessory regulatory binding sites on the enzyme surface. The inibitors are efficacious in several experimental models of thrombosis, and above all, illustrate the feasibility of low molecular weight protein mimetics. 

It is important to note that the interaction with regulatory binding sites at the chloride channels does not involve making or breaking covalent bonds. Pesticides of this class may therefore be rather stable. 

Inhibition of a regulatory enzyme by a feedback inhibitor does not conform to any normal inhibition pattern, and the feedback inhibitor F bears little structural similarity to A, the substrate for the regulatory enzyme. F apparently acts at a binding site distinct from the substrate-binding site. The term allosteric is apt, because F is sterically dissimilar and, moreover, acts at a site other than the site for S. Its effect is called allosteric Inhibition. 

Muscle glycogen phosphorylase is a dimer of two identical subunits (842 residues, 97.44 kD). Each subunit contains a pyridoxal phosphate cofactor, covalently linked as a Schiff base to Lys °. Each subunit contains an active site (at the center of the subunit) and an allosteric effector site near the subunit interface (Eigure 15.15). In addition, a regulatory phosphorylation site is located at Ser on each subunit. A glycogen-binding site on each subunit facilitates prior association of glycogen phosphorylase with its substrate and also exerts regulatory control on the enzymatic reaction. 

Adenylyl Cyclases. Figure 4 Regulation of adenylyl cyclases by G-proteins. Abbreviations Hs, Hj, Rs, and Rj denote hormones and receptors that lead to stimulation or inhibition, respectively, of adenylyl cyclases, Ca and Ci are active and inactive configurations of adenylyl cyclase, Fo forskolin binding site, Gs and Gj are GTP-dependent regulatory proteins comprising their respective as, and (3y subunits. 

A model called histone code theory includes more aspects of chromatin regulation which have been identified. The histone code theory predicts that histone acetylation and other posttranslational histone modifications serve as binding sites for regulatory proteins which mediate processes like gene transcription upon recruitment (see Fig. 2b) [3]. In this context histone modifications can be understood as... 

The site level at which [Ca2+]i regulates NCX activity (CBD) is different from the one required for Ca2+ transport. Submicromolar concentrations (0.1-0.3 pM) of intracellular Ca2+ are needed to activate the antiporter through these Ca2+ binding site. The location of such regulatory site has been identified in the 134-amino acid-length region, situated in the center of the intracellular f loop [2], (Table 1)... 

TPR) domains. PP2B (calcineurin) is a heterodimer of a catalytic A-subunit together with a regulatory, Ca2+-binding B-subunit. The A-subunit additionally carries a calmodulin binding site and an autoinhibitory domain. PP7 also contains EF-hand motifs. Both, PP2B and PP7 are stimulated by Ca2+-ions. 

The 80-bp right operator. Op, can be subdivided into three discrete, evenly spaced, 17-bp cis-active DNA elements that represent the binding sites for either of two bacteriophage A, regulatory proteins. Impor-... 

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