Inhibitor binding three-dimensional structure

The two isozymes are both homodimers, composed of approximately 600 amino acids and possess approximately 60% homology. The three-dimensional structures of COX-1 and COX-2 are very similar. Each one consists of three independent units an epidermal growth factor-like domain, a membrane-binding section and an enzymic domain. The catalytic sites and the residues immediately adjacent are identical but for two small but crucial variations that result in an increase in the volume of the COX-2-active site, enabling it to accept inhibitor-molecules larger than those that could be accommodated in the COX-1 molecule. 

This example is one where the accurate three-dimensional structure of the protein is unknown under these circumstances, it is necessary to create a computer model. The development of inhibitors that are designed to overcome the effects of this mutation could not be based on the accurate structure of a ligand-binding site here, ligand-based design would be appropriate (see Sect. 7.9). 

If an inhibitor binds not only to free enzyme but also to the enzyme substrate complex ES, inhibition is noncompetitive. In this case, S and I do not mutually exclude each other and both can be bound to the enzyme at the same time. Why does such an inhibitor slow an enzymatic reaction In most instances, the structure of the inhibitor does not show a close similarity to that of substrate, which suggests that the binding of inhibitors is at an allosteric site, that is, at a site other than that of the substrate. The inhibition of the enzyme may result from a distortion of the three-dimensional structure of the enzyme which is caused by the binding of the inhibitor. This distortion may be... 

The RGD motif has long been known to be the principal binding motif of several integrins (77). Aumailly et al. showed that the cyclic peptide c(RGDfV), where f denotes d-phenylalanine (D-Phe), is a potent inhibitor of the integrin aubfo and determined the three-dimensional structure of the cyclic peptide from... 

Protein explorer is one of the most widely used visualization tools for protein structures. Protein Explorer is free software for visualizing the three-dimensional structures of protein, DNA, and RNA macromolecules, and their interactions and binding of ligands, inhibitors, and drugs. Protein explorer is easy to use, free, and widely used. It can be used be novice users as well as experts. The RasMol website has been visited by over 250,000people from 115 countries. 

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