Binding regions

Most effective differentiation of the receptor between substrates will occur when multiple interactions are involved in the recognition process. The more binding regions (contact area) present, the stronger and more selective will be the recognition (17). This is the case for receptor molecules that contain intramolecular cavities, clefts or pockets into which the substrate may fit (Fig. 1). 

Fig. 13. Structure of the bleomycin-Fe(II)-02 complex showing the DNA binding region.

Table 8.1 The nucleotide sequences of the three protein-binding regions ORl, OR2, and OR3 of the operator of bacteriophage lambda...

Approximately 10 base pairs are required to make one turn in B-DNA. The centers of the palindromic sequences in the DNA-binding regions of the operator are also separated by about 10 base pairs (see Table 8.1). Thus if one of the recognition a helices binds to one of the palindromic DNA sequences, the second recognition a helix of the protein dimer is poised to bind to the second palindromic DNA sequence. 

Homeoboxes code for homeodomains, sequences of 60 amino acids that function as the DNA-binding regions of transcription factors. Each homeo-box gene in Drosophila is expressed only in its own characteristic subset of embryonic cells, and almost every embryonic cell contains a unique combination of homeodomain proteins. 

Figure 9.13 The DNA-binding region of the protein Oct-1, the POU region (green), comprises two domains, the POU-specific domain (dark green) and the POU homeodomain (light green) joined by a linker region (blue). These two domains bind to DNA in a tandem arrangement.

Helix-loop-helix (b/HLH) transcription factors are either heterodimers or homodimers with basic a-helical DNA-binding regions that lie across the major groove, rather than along it, and these helices extend into the four-helix bundle that forms the dimerization region. A modification of the b/HLH structure is seen in some transcription factors (b/HLH/zip) in which the four-helix bundle extends into a classic leucine zipper. 

Figure 11.9 A diagram of the active site of chymotrypsin with a bound inhibitor, Ac-Pro-Ala-Pro-Tyr-COOH. The diagram illustrates how this inhibitor binds in relation to the catalytic triad, the strbstrate specificity pocket, the oxyanion hole and the nonspecific substrate binding region. The Inhibitor is ted. Hydrogen bonds between Inhibitor and enzyme are striped. (Adapted from M.N.G. James et al., /. Mol. Biol. 144 43-88, 1980.)...

Figure 11.10 Topological diagram of the two domains of chymotrypsin, illustrating that the essential active-site residues are part of the same two loop regions (3-4 and 5-6, red) of the two domains. These residues form the catalytic triad, the oxyanion hole (green), and the substrate binding regions (yellow and blue) including essential residues in the specificity pocket.

The C-terminal part is green. The catalytic triad Asp 32, His 64, and Ser 221 as well as Asn 15S, which forms part of the oxyanion hole are shown in purple. The main chain of part of a polypeptide Inhibitor is shown in red. Main-chain residues around 101 and 127 (orange circles) form the nonspecific binding regions of peptide substrates. 

Figure 13.19 Ribbon diagram of the stmcture of the extracellular domain of the human growth hormone. The hormone-binding region is formed by loops (yellow) at the hinge region between two fibronectin type III domains. (Adapted from J. Wells et al., Annu. Rev.

Die cytosolic loop between TMs 13 and 14 (KCO I) and TMs 16-17 (KCO II) were identified as critical for KatpCO binding to SURs (Fig. 4d). T1286 and Ml 290 appeared to be particularly important. Close local association of sulfonylurea and KCO binding regions might represent the structural basis for negative allosteric coupling of the sites. 

Figure 2. Schematic of HSFl map depicting the DNA binding region at the amino terminus and the regulatory regions for protein-protein interactions in the COOH-ter-...

Alternatively, one interesting drug delivery technique exploits the active transport of certain naturally-occurring and relatively small biomacromolecules across the cellular membrane. For instance, the nuclear transcription activator protein (Tat) from HIV type 1 (HlV-1) is a 101-amino acid protein that must interact with a 59-base RNA stem-loop structure, called the traus-activation region (Tar) at the 5 end of all nascent HlV-1 mRNA molecules, in order for the vims to replicate. HIV-Tat is actively transported across the cell membrane, and localizes to the nucleus [28]. It has been found that the arginine-rich Tar-binding region of the Tat protein, residues 49-57 (Tat+9 57), is primarily responsible for this translocation activity [29]. 

A 3D model of the fibrinogen-derived (very late antigen-4, VLA-4) inhibitor 4-[N -(2-methylphenyl)ureido]phenylacetyl-Leu-Asp-Val was derived from the X-ray structure of the related integrin-binding region of the vascular cell adhesion molecule-1 (VCAM-1). A 3D pharmacophore was generated with the program Catalyst, and a 3D search was performed in 8624 molecules from... 

LDL (apo B-lOO, E) receptors occur on the cell surface in pits that are coated on the cytosolic side of the cell membrane with a protein called clathrin. The glycoprotein receptor spans the membrane, the B-lOO binding region being at the exposed amino terminal end. After binding, LDL is taken up intact by endocytosis. The apoprotein and cholesteryl ester are then hydrolyzed in the lysosomes, and cholesterol is translocated into the cell. The receptors are recycled to the cell surface. This influx of cholesterol inhibits in a coordinated manner HMG-CoA synthase, HMG-CoA reductase, and, therefore, cholesterol synthesis stimulates ACAT activ-... 

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