Background & Aims: Many neurodegenerative diseases including Alzheimer’s, Parkinson and Huntington diseases are associated with the deposition proteinaceous aggregates known as amyloid fibrils. Currently, there is no approved therapeutic agent for inhibition of fibrillar assemblies. One important approach in the development of therapeutic agents is the use of herbal extracts. At the present com...

amyloid pathology is associated with fibril aggregation of different proteins which results in the progressive damage of affected organs. it is strongly believed that specific small molecules interfere with fibrillation by interacting with the amyloidogenic proteins. we had previously reported the strong and long-term inhibition of fibrillation of hen egg white lysozyme (hewl) by cuminum cyminu...

Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations indicate that the reaction of native HEWL with its natural substrate involves a covalent intermediate, in contrast to the 'textbook' mechanism for this seminal enzyme.

Alanine scanning mutagenesis of the HyHEL-10 paratope of the HyHEL-10/HEWL complex demonstrates that the energetically important side chains (hot spots) of both partners are in contact. A plot of deltadeltaG(HyHEL-10_mutant) vs. deltadeltaG(HEWL_mutant) for the five of six interacting side-chain hydrogen bonds is linear (Slope = 1). Only 3 of the 13 residues in the HEWL epitope contribute >4 kc...

The rate constants, k,,, for the formation of hen (chicken) lysozyme (HEWL) .Fab-lO complexes have been determined for wild-type (WT) and epitope-mutated lysozymes by a homogeneous solution method based on the 95% reduced enzymatic activity of the complex. The values fall within a narrow IO-fold range [(0.18 to 1.92) X lo6 M" s I 1. The affinity constants, KO. cover a broader, 440-fold, range f...