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Chaperone-like effect of ceftriaxone on HEWL aggregation: A spectroscopic and computational study
- Source :
- Biochimica et biophysica acta. G, General subjects, 1862 (2018): 1317–1326. doi:10.1016/j.bbagen.2018.02.014, info:cnr-pdr/source/autori:Ruzza, Paolo; Vitale, Rosa Maria; Hussain, Rohanah; Montini, Alessia; Honisch, Claudia; Pozzebon, Alice; Hughes, Charlotte S.; Biondi, Barbara; Amodeo, Pietro; Sechi, GianPietro; Siligardi, Giuliano/titolo:Chaperone-like effect of ceftriaxone on HEWL aggregation: A spectroscopic and computational study/doi:10.1016%2Fj.bbagen.2018.02.014/rivista:Biochimica et biophysica acta. G, General subjects (Print)/anno:2018/pagina_da:1317/pagina_a:1326/intervallo_pagine:1317–1326/volume:1862
- Publication Year :
- 2018
- Publisher :
- Elsevier Scientific Publ. Co., Amsterdam , Paesi Bassi, 2018.
-
Abstract
- Background Lysozyme is a widely distributed enzyme present in a variety of tissue and body fluids. Human and hen egg white lysozyme are used as validated model to study protein folding and stability and to understand protein misfolding and aggregation. We recently found that ceftriaxone, a β-lactam antibiotic able to overcome the blood-brain barrier, successfully eliminated the cellular toxic effects of misfolded proteins as Glial Fibrillary Acidic Protein (GFAP) and α-synuclein. To further understand the anti-amyloidogenic properties of ceftriaxone, we studied its activity towards lysozyme aggregation with the aim to investigate a possible chaperone-like activity of this molecule. Methods Here we present the results obtained from fluorescence and synchrotron radiation circular dichroism spectroscopies and from molecular docking and molecular dynamics about the lysozyme-ceftriaxone interaction at neutral and acidic pH values. Results We found that ceftriaxone exhibits comparable affinity constants to lysozyme in both experimental pH conditions and that its addition enhanced lysozyme stability reducing its aggregation propensity in acidic conditions. Computational methods allowed the identification of the putative binding site of ceftriaxone, thus rationalizing the spectroscopic results. Conclusions Spectroscopy data and molecular dynamics indicated a protective effect of ceftriaxone on pathological aggregation phenomena suggesting a chaperone-like effect of this molecule on protein folding. General significance These results, in addition to our previous studies on α-synuclein and GFAP, confirm the property of ceftriaxone to inhibit the pathological protein aggregation of lysozyme also by a chaperone-like mechanism, extending the potential therapeutic application of this molecule to some forms of human hereditary systemic amyloidosis.
- Subjects :
- 0301 basic medicine
Protein Folding
spectroscopy
Protein Conformation
Lysozyme
Biophysics
Molecular Dynamics Simulation
Protein aggregation
Molecular dynamics
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Animals
Humans
Binding site
Misfolding diseases
Molecular Biology
chemistry.chemical_classification
Binding Sites
Glial fibrillary acidic protein
biology
Chemistry
Ceftriaxone
Computational Biology
Hydrogen-Ion Concentration
Molecular Docking Simulation
030104 developmental biology
Enzyme
Chaperone (protein)
Molecular docking
biology.protein
Synchrotron radiation circular dichroism
Muramidase
Protein folding
Protein Multimerization
Molecular Chaperones
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta. G, General subjects, 1862 (2018): 1317–1326. doi:10.1016/j.bbagen.2018.02.014, info:cnr-pdr/source/autori:Ruzza, Paolo; Vitale, Rosa Maria; Hussain, Rohanah; Montini, Alessia; Honisch, Claudia; Pozzebon, Alice; Hughes, Charlotte S.; Biondi, Barbara; Amodeo, Pietro; Sechi, GianPietro; Siligardi, Giuliano/titolo:Chaperone-like effect of ceftriaxone on HEWL aggregation: A spectroscopic and computational study/doi:10.1016%2Fj.bbagen.2018.02.014/rivista:Biochimica et biophysica acta. G, General subjects (Print)/anno:2018/pagina_da:1317/pagina_a:1326/intervallo_pagine:1317–1326/volume:1862
- Accession number :
- edsair.doi.dedup.....f9148da43c32c2712a4e5feb49ea641d