Primary binding

Table 17.1 Phage-optimized sequences of Kunitz domain libraries primary binding loop...

Tetracycline has a secondary binding site in the H27 switch region that may also be fimctionally significant. The dtug binds at the interface of the three domains of 16S rRNA, close to helix 44 and between helices 11 and 27. As with the primary binding site, contacts are made from the hydrophilic face of the dtug to the backbone of 16S rRNA. In this binding site, tetracycline may function to stabilize the ram state. 

Ribosomal Protein Synthesis Inhibitors. Figure 3 The chemical structure of tetracycline and possible interactions with 16S rRNA in the primary binding site. Arrows with numbers indicate distances (in A) between functional groups. There are no interactions obseived between the upper portion of the molecule and 16S rRNA consistent with data that these positions can be modified without affecting inhibitory action (from Brodersen et al. [4] with copynght permission). 

Human leukocyte elastase is a protease that degrades elastin and other connective tissue components. It is implicated in the pathogenesis of pulmonary emphysema and other inflammatory diseases such as rheumatoid arthritis and cystic fibrosis. Porcine pancreatic elastase has often been used as a model for HLE. Both enzymes have a small primary binding site Si. 

The simplest model that can describe allosteric interactions at GPCRs is the ternary complex allosteric model [9], As shown in Figure 1, according to this model two parameters define the actions of allosteric agent (X) its affinity for the unoccupied receptor (Kx) and its cooperativity (a) with the ligand (A) that interacts at the primary binding site a < 1 represents negative cooperativity a = 1, no cooperativity a > 1, positive cooperativity. 

The inner face of the activated receptor binds to the C-terminus of the G-protein a subunit (see Figure 7.3). Inner loop 3 (ic3) between transmembrane helices 5 and 6 of the receptor plays a critical role in this interaction. Note, however, that although the a subunit bears the primary binding site for the receptor, attachment of the py-dnner to the a subunit is essential for this interaction to occur. 

The primary binding site of adenine is N(9) but when this is blocked as in adenosine it becomes N(l). This makes the binding of metals to adenosine weaker than the binding to N(7) of guanosine. The N(7) of guanosine is a known major site of alkylation too. 

Electron transfer from Fe(II)cytc to ccp(ES) proceeds with a rate of 800 s at — AG° = 0.90 eV [73]. From measurements of ET rates at other driving forces, the cyt c/ccp reorganization energy was estimated to be 1.5 eV the relatively large X value may be a result of redox-dependent fluctuations of the protein-protein orientation, since the primary binding mode is electrostatic (salt bridges) [73]. 

Because of the similarity between the X-ray crystal structure of GH5 (the globular domain of H5) and that of the helix-turn-helix protein CAP (bacterial Catabolite Activator Protein), for which the structure of the complex with DNA has been solved [11], it has been suggested that the primary binding site on GHl... 

Figure 3. Stereoscopic projections of the complex between the trimannoside and ConA, with the a(l- 6)-linked terminal mannose in the primary binding site Binding mode (i). Details of the possible hydrogen bonds are given in Table IV.

Table IV. Hydrogen bonds between ConA and the trimannoside, a(l- 6)-linked mannose residue in primary binding site...

Thus the present study shows that ConA interacts with the trimannosidic core by binding preferentially to the a(1- 6)-linked terminal mannose residue at the primary binding site. Depending on the orientation of the a(l- 6) terminal residue in the primary binding site the a(l- 3) terminal mannose residue interacts either with Tyr 100 or His 205 on the surface of ConA (Figures 3 and 4). This indicates that there is no specific extended binding site... 

Micafungin is highly (more than 99%) protein bound in vitro, independent of plasma concentrations over the range of 10 to 100 mcg/mL. The primary binding protein is albumin however, micafungin, at therapeutically relevant... 

Although comprehensive structural analyses of ATP binding sites are not yet available, it is clear that the primary binding interactions usually originate from hydrophobic... 

---