Figure 11.

A model to account for phosphatidylinositol desensitization of ATP inhibition of K_ATP. The ATP molecule is shown as a stick diagram having an ∼120° angle between the adenosine group (ring structures) and the phosphate group (crosshatched end). The protein binding site is depicted as a “hook” with positively charged residues, indicated by ⊕, representing the site for electrostatic interaction with the negatively charged phosphates, and the hook representing a hydrophobic binding site for the adenine moiety. K^A denotes the association constant of the step in which a complex of ATP and channel is formed through the binding of the hydrophilic phosphate group, and K^B denotes the association constant of the step forming the complex through the binding of the hydrophobic adenosine moiety. These steps are bimolecular bindings presumably with the same binding constants of the individual parts binding to their binding site. K^Au and K^Bu are the association constants of the subsequent binding of the second part of the ATP molecule to the binding site, which is a unimolecular (thus the u in the superscript) process. Binding of PPIs to the charged part of the ATP binding site (denoted in the diagram as negatively charged heads with tails pointing downward) causes a decrease rate of ATP association involving phosphate group (denoted by an apostrophe and smaller arrows). The rightmost state represents the state in which both parts of the ATP molecule are bound to the binding site. The states with adenosine binding to the site (bottom and right) are proposed to cause nonconducting channels.