text: INSTIs bind tightly and specifically to the IN that is associated with the ends of the DNA by chelating the divalent metal ions (Mg) which is coordinated by the catalytic triad i.e. the DDE motif. The DDE motif is located in the CCD of IN and is the active site of the enzyme and hence INSTIs are so called active site inhibitors. INSTIs bind to a specific site close to the DDE motif of IN, a site that is present only in the conformation that occurs after processing of the 3´ viral DNA ends. Viral DNA may well form a part of the inhibitor binding site. The binding is a form of allosteric inhibition as it implies blockage of a specific integrase-viral DNA complex. This results in selective inhibition of the strand-transfer reaction, with no significant effect on the 3´-processing reaction. INSTIs may therefore be more specific and bind selectively to the target DNA binding site and hence be less toxic than bifunctional inhibitors that are able to bind to both the donor and target binding sites.
  INBIs also bind to IN but the mechanism of action is unknown so the binding can not be detailed.