Evidence for Inhibition of Lysozyme Amyloid Fibrillization by Peptide Fragments from Human Lysozyme: A Combined Spectroscopy, Microscopy, and Docking Study.
Degenerative diseases, such as Alzheimer's and prion diseases, as well as type II diabetes, have a pathogenesis associated with protein misfolding, which routes with amyloid formation. Recent strategies for designing small-molecule and polypeptide antiamyloid inhibitors are mainly based on mature fibril structures containing cross β-sheet structures. In the present study, we have tackled the hypothesis that the rational design of antiamyloid agents that can target native proteins might offer advantageous prospect to design effective therapeutics. Lysozyme amyloid fibrillization was treated with three different peptide fragments derived from lysozyme protein sequence R(107)-R(115). Using low-resolution spectroscopic, high-resolution NMR, and STD NMR-restrained docking methods such as HADDOCK, we have found that these peptide fragments have the capability to affect lysozyme fibril formation. The present study implicates the prospect that these peptides can also be tested against other amyloid-prone proteins to develop novel therapeutic agents.
Department of Biophysics, Bose Institute , P-1/12 CIT Scheme VII (M), Kolkata 700054, India.
Rajiv K
RK
Kar
Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences , Watsonova 47, 040 01 Kosice, Slovakia.|Department of Medical and Clinical Biochemistry Faculty of Medicine, Safarik University , Trieda SNP 1, 040 11 Kosice, Slovakia.
Zuzana
Z
Gazova
Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences , Watsonova 47, 040 01 Kosice, Slovakia.|Department of Biochemistry, Institute of Chemistry, Faculty of Science, Safarik University , Srobarova 2, 041 54 Kosice, Slovakia.
Zuzana
Z
Bednarikova
Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
Kamal H
KH
Mroue
Department of Biophysics, Bose Institute , P-1/12 CIT Scheme VII (M), Kolkata 700054, India.
Anirban
A
Ghosh
RI-B-NT Research Institute of Bioinformatics and Nanotechnology, Franziusallee 177, 24148 Kiel, Germany.
Ruiyan
R
Zhang
Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences , Watsonova 47, 040 01 Kosice, Slovakia.|Institute of Biology and Ecology, Faculty of Science, Safarik University , Srobarova 2, 041 54 Kosice, Slovakia.
Katarina
K
Ulicna
RI-B-NT Research Institute of Bioinformatics and Nanotechnology, Franziusallee 177, 24148 Kiel, Germany.
Hans-Christian
HC
Siebert
N. D. Zellinsky Institute of Organic Chemistry, Russian Academy of Sciences , 119991 Moscow, Russian Federation.
Nikolay E
NE
Nifantiev
Department of Biophysics, Bose Institute , P-1/12 CIT Scheme VII (M), Kolkata 700054, India.
Anirban
A
Bhunia
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D002942:Circular Dichroism; D018625:Microscopy, Atomic Force; D062105:Molecular Docking Simulation; D009113:Muramidase / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence
D000682:Amyloid; D010446:Peptide Fragments; D009113:Muramidase