Structure common binding groups

Figure 4-20 Models of competitive inhibition S and I are mutually exclusive. (1) Classical model. S and 1 compete for the same binding site. I must resemble S structurally. (2) I and S are mutually exclusive because of steric hindrance. (3) I and S share a common binding group on the enzyme. (4) The binding sites for I and S are distinct, but overlapping. (5) The binding of I to a distinct inhibitor site causes a conformational change In the enzyme that distorts or masks the substrate binding site (and vice versa).

At first glance, the structure of these macrocycles may appear very different from classical HD AC inhibitors. However, they share the same common features the macrocyclic structure comprises the surface recognition element, which is connected to the metal-binding group via a relatively flexible linker moiety. Notably, reductive cleavage of the disulfide bond in romidepsin is required to liberate a mercapto group that can bind the zinc ion within the catalytic site. 

A summary of known binding constants for Pb(II) to common functional groups, biological molecules, macrocycles, and chelation therapy agents is provided in Tables IX-XI (264, 270, 306, 315-329). Structures of chelating ligands and macrocycles discussed in the text are presented in Table VIII. 

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