Structure of the Binding Site

Another example of the shape similarity effect on molecular recognition involves the similarity between the structures of the binding sites. Investigation was made for four reaction systems I-IV each consisting of a 1 1 mixture of thiols HS—X and HS—Y... 

A receptor is a surface membrane component, usually a protein, which regulates some biological event in response to reversible binding of a relatively small molecule40 . The precise three-dimensional structures of the binding sites of receptors still remain unknown today. Thus, this section mainly describes the correlation of shape similarity between the molecules which would bind to a given receptor with their biological activity. 

Even if the structure of the binding site on the enzyme or the structure of the receptor is known, finding of lead structures remains a difficult challenge. In general, one proceeds as follows ... 

Smerdon, S. J., Jager, J., Wang, J., Kohlstaedt, L. A., Chirino, A.J., Friedman, J. M., Rice, P. A., and Steitz, T. A. (1994). Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. Proc. Natl. Acad. Sd. USA91, 3911-3915. 

To what extent do the solution complexes formed between the monomer and the template in solution reflect the architecture of the polymeric binding sites This question is important, since a thorough characterisation of the monomer-template assemblies may assist in deducing the structure of the binding sites in the polymer and thus have a predictive value. 

The synthesis of ODNs bearing two pyrene residues attached to the 5 -phosphate has been investigated. Excimer fluorescence intensity is highly sensitive to duplex formation, such that on hybridisation with either DNA or RNA the fluorescence intensity increases ten-fold. Changes in excimer fluorescence are also dependent on the structure of the binding site. Hybridisation to structured targets leads to a quenching of the fluorescence, and therefore these probes may... 

X-ray crystal structure of the binding site of a mutant mannose binding protein with specificity for sialyl Lewis X with ligand bound. See text for details. (Reprinted with permission from [30])... 

Figure 20.4 X-ray structures of the binding sites of the Abl kinase/imatinib and cytochrome P450 3A4 /erythromycin complexes (PDB Protein Data Bank). The amino acids located within 4A of ligands are depicted. The hydrogen bonding interactions are shown by dashed lines, and the amino acids participating in hydrogen-bonding interactions are labeled in bold. The images were produced with Pymol (DeLano Scientific LLC). See color plates.

---