title: Competitive inhibition reaction mechanisms for the two-step model of protein aggregation.
abstract: We propose three new reaction mechanisms for competitive inhibition of protein aggregation for the two-step model of protein aggregation. The first mechanism is characterized by the inhibition of native protein, the second is characterized by the inhibition of aggregation-prone protein and the third mechanism is characterized by the mixed inhibition of native and aggregation-prone proteins. Rate equations are derived for these mechanisms, and a method is described for plotting kinetic results to distinguish these three types of inhibitors. The derived rate equations provide a simple way of estimating the inhibition constant of native or aggregation-prone protein inhibitors in protein aggregation. The new approach is used to estimate the inhibition constants of different peptide inhibitors of insulin aggregation.
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Whidden
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Ho
authors.affiliation: Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Magdalena I
authors.initials: MI
authors.lastname: Ivanova
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, MI 48105, USA. Electronic address: schnells@umich.edu.
authors.forename: Santiago
authors.initials: S
authors.lastname: Schnell
mesh_terms: D000595:Amino Acid Sequence; D001667:Binding, Competitive; D006801:Humans; D007328:Insulin / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D066329:Protein Aggregates; D011485:Protein Binding
chemical_list: D007328:Insulin; D010455:Peptides; D066329:Protein Aggregates
keywords: Distinguishing inhibition mechanism; Inhibition; Kinetic result analysis; Parameter estimation; Protein aggregation; Reaction mechanism