Binding properties

The first two properties of steroid receptors, i.e., the binding affinity and capacity are derived from binding curves. The interaction between a steroid and its receptor 

Substituting [B] for the concentration of bound steroid, [F] for the concentration of free steroid, and [Rtot] = [R] + [SR] for the total number of receptor sites, this relationship can be rewritten as  

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While a number of proteins have been crystallized in this manner, the majority of studies have focused on a robust system comprising the tetrameric protein streptavidin and the vitamin biotin. The choice of this system is primcirily motivated by the strong bond between biotin and streptavidin (having an association equilibrium constant, Ka Tbe binding properties were recently... 

Experimental techniques based on the application of mechanical forces to single molecules in small assemblies have been applied to study the binding properties of biomolecules and their response to external mechanical manipulations. Among such techniques are atomic force microscopy (AFM), optical tweezers, biomembrane force probe, and surface force apparatus experiments (Binning et al., 1986 Block and Svoboda, 1994 Evans et ah, 1995 Israelachvili, 1992). These techniques have inspired us and others (see also the chapters by Eichinger et al. and by Hermans et al. in this volume) to adopt a similar approach for the study of biomolecules by means of computer simulations. 

A fuzzier atom type participating in these descriptors has been defined that is pharmacologically relevant - the physicochemical type at near-neutral pH [24], which is one of the following seven binding property classes 1 = cation 2 = anion 3 = neutral hydrogen-bond donor 4 = neutral H-bond acceptor ... 

The atom pair (ap) and topological torsion (U) descriptors and their fuzzy binding property analogs bp and bt are again selected for illustrative purposes [24, 25]. 

Added Water. Frankfurters and bologna are allowed to contain combinations of fat and added water not to exceed 40% with a maximum fat content of 30%. This allows, for example, a 10% fat frankfurter to be produced with 30% added water. Substitution of large amounts of fat with water alone may not give the optimal sensory and textural properties that consumers want (43). To overcome these shortcomings, several binders can be added to improve water and fat-binding properties, cooking yields, texture, and flavor (27). 

The 434 Cro molecule contains 71 amino acid residues that show 48% sequence identity to the 69 residues that form the N-terminal DNA-binding domain of 434 repressor. It is not surprising, therefore, that their three-dimensional structures are very similar (Figure 8.11). The main difference lies in two extra amino acids at the N-terminus of the Cro molecule. These are not involved in the function of Cro. By choosing the 434 Cro and repressor molecules for his studies, Harrison eliminated the possibility that any gross structural difference of these two molecules can account for their different DNA-binding properties. 

The polypeptide chain of p53 is divided in three domains, each with its own function (Figure 9.16). Like many other transcription factors, p53 has an N-terminal activation domain followed by a DNA-binding domain, while the C-terminal 100 residues form an oligomerization domain involved in the formation of the p53 tetramers. Mutants lacking the C-terminal domain do not form tetramers, but the monomeric mutant molecules retain their sequence-specific DNA-binding properties in vitro. 

In this chapter we will examine the construction principles of spherical viruses, the structures of individual subunits and the host cell binding properties of the surface of one of the picornaviruses, the common cold virus. 

The classic zinc fingers, the DNA-binding properties of which are discussed in Chapter 10, are small compact domains of about 30 residues that fold into an antiparallel p hairpin followed by an a helix. All known classic zinc fingers have a zinc atom bound to two cysteines in the hairpin and two histidines in the helix, creating a sequence motif common to all zinc finger genes. In the absence of zinc the structure is unfolded. 

In more recent work, Lockhart and Thompson have formed derivatives of 3 by substituting the secondary nitrogen. Substituents include CO—CH2—CH2—CH2—COOH and CH2CH2CH2 0Et. The latter compound should exhibit quite interesting binding properties for alkali metals, but binding constants for these compounds do not appear to have been determined. 

A number of bridged crown ethers have been prepared. Although the Simmons-Park in-out bicyclic amines (see Sect. 1.3.3) are the prototype, Lehn s cryptands (see Chap. 8) are probably better known. Intermediates between the cryptands (which Pedersen referred to as lanterns ) and the simple monoazacrowns are monoazacrowns bridged by a single hydrocarbon strand. Pedersen reports the synthesis of such a structure (see 7, below) which he referred to as a clam compound for the obvious reason . Although Pedersen appears not to have explored the binding properties of his clam in any detail, he did attempt to complex Na and Cs ions. A 0.0001 molar solution of the clam compound is prepared in ethanol. The metal ions Na and Cs are added to the clam-ethanol solutions as salts. Ultraviolet spectra of these solutions indicate that a small amount of the Na is complexed by the clam compound but none of the Cs . 

Although the first all-sulfur macrocycles were prepared many years ago " the first systematic study of such compounds was initiated by Busch and his coworkers , who were interested in the cation binding properties of such ligands. A sequential synthesis was utilized to produce 1,4,8,11-tetrathiacyclotetradecane [tetrathia-14-crown-4 (70)] . In the first step, 1,3-propanedithiol is metallated using sodium and alkylated with 2-chloroethanol. The diol was then treated with thiourea to form the dimercapto-dithioether compound 9. The latter was once again metallated with sodium and allowed to react with 1,3-dibromopropane. The yield of 70 in the ring closure step, conducted at high dilution in absolute ethanol, was 7.5% after recrystallization. The entire sequence is illustrated in Eq. (6.8) . ... 

A good deal of work has been done on polymeric crown ethers during the last decade. Hogen Esch and Smid have been major contributors from the point of view of cation binding properties, and Blasius and coworkers have been especially interested in the cation selectivity of such species. Montanari and coworkers have developed a number of polymer-anchored crowns for use as phase transfer catalysts. Manecke and Storck have recently published a review titled Polymeric Catalysts , which may be useful to the reader in gaining additional perspective. 

X 10 forNa+,2.8 X 10 for, and 1.3 x 10 for Li These constants were of a magnitude that persuaded the authors to liken the binding properties of these calixar-enes to cryptands and spherands. 

Chang and coworkers [10] have synthesized amide derivatives of calixarenes and examined their ion binding properties with Group I and Group II cations. They observed that although the amides are much less effective than the esters for the complexation of Group I cations they are more effective for Group II cations. 

Application of Cation and Anion Binding Properties of Macrocyclic Polyamines... 

DeLean, A., Stadel, J. M. Lefkowitz, R. J. (1980). A ternary complex model explains the agonist-specific binding properties... 

Choi, H., Tang, C.-K., and Tu, S. C. (1995). Catalytically active forms of the individual sub-units of Vibrio harveyi luciferase and their kinetic and binding properties./. Biol. Ghent. 270 16813-16819. 

Matthews, J. C., Hori, K., and Cornier, M. J. (1977b). Substrate and substrate analogue binding properties of Renilla luciferase. Biochemistry 16 5217-5220. 

Shin JM, S achs G (2004) Differences in binding properties of two proton pump inhibitors on the gastric H+,K+-ATPase in vivo. Biochem Pharmacol 68 2117-2127... 

Most hormones and neurotransmitters can interact with more than one receptor subtype. The different receptor isoforms may differ in their ligand-binding properties,... 

Like VEGF165, native VEGF is a heparin-binding homodimeric glycoprotein of 45 kDa. In contrast, VEGFi2i lacks heparin-binding properties. VEGF i89... 

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