LIGAND-BINDING TO WILD-TYPE AND E-B13Q MUTANT INSULINS - A 3-STATE ALLOSTERIC MODEL SYSTEM SHOWING HALF-SITE REACTIVITY

By using ultra-violet and visible absorbance in conjunction with high field H-1-nuclear magentic resonance spectroscopy, the insulin hexamer has been shown to undergo two allosteric transitions in solution invo lving three allosteric states (T-6 reversible arrow T-3 R(3) reversibl e arrow R(6)). A simple mathematical model consisting of four variable s has been derived that quantitatively describes the complex homotropi c and heterotropic interactions that modulate these allosteric transit ions. The mutation of one residue, Glu-B13 to Gin, results in an unexp ected change in the T(3)R(3) to R(6) equilibrium by a factor of 10(7).