Docked active site regions

The two docked active site regions (with MTX bound) are shown in Figure 12. Examination of the docked active sites reveals that there are three general types of amino acid residues involved in the construction of the active site surface ... 

Consider enzymes. Enzymes are proteins that act as catalysts in biochemical reactions. They are able to do this because enzyme molecules contain one or more active sites, regions with a characteristic shape designed to fit some particular molecule (the substrate) on which the enzyme operates. Suppose the function of the enzyme is to break apart a large molecule. That reaction is made possible when the large molecule "docks in the active site, prompting some chemical mechanism in or around the active site that cleaves it. If the function of the enzyme is to join two small molecules, the reaction takes place when both small molecules take their places in the active site, which generates chemical bonds between the two molecules. 

In addition, Ji et al. docked 25 NOS inhibitors into the active site to understand the interaction mode of the inhibitors with the active site and also to understand the importance of the MIF differences in the active site for the isoform selectivity. In general, the experimental selectivities of the ligands agreed well with the derived selectivity regions. However, as the authors point out, the selectivity of some inhibitors with unusual kinetic behavior or even covalent binding to the target cannot be explained with the CPCA method. 

Thus far, no potent ATP competitive inhibitors of ERKl/2 have been reported. Because of the likely cross-reactivity of ATP competitive inhibitors, compounds that inhibit through interactions outside the ATP binding pocket are attractive. Substrates bind to MAPKs on the opposite face from the active site in a region, which are sometimes called the common docking or CD site this site can also influence kinase conformation (21). Small molecule inhibitors that bind to the CD site of ERK2 have been identified recently but have not received extensive testing (23). 

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