Polyamines and its analogue modulates amyloid fibrillation in lysozyme: A comparative investigation.
Amyloid
/ metabolism
Amyloidosis
/ metabolism
Animals
Avian Proteins
/ metabolism
Biogenic Polyamines
/ metabolism
Chickens
/ metabolism
Hydrophobic and Hydrophilic Interactions
Molecular Docking Simulation
Muramidase
/ metabolism
Protein Aggregates
Protein Aggregation, Pathological
/ metabolism
Spermidine
/ metabolism
Spermine
/ analogs & derivatives
1-napthyl acetyl spermine (NASPM)
Amyloidosis
Atomic force microscopy
Lysozyme
Neurodegenerative diseases
Polyamine
Protein aggregation
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
10
05
2019
revised:
03
01
2020
accepted:
07
02
2020
pubmed:
12
2
2020
medline:
21
10
2020
entrez:
12
2
2020
Statut:
ppublish
Résumé
Polyamines can induce protein aggregation that can be related to the physiology of the cellular function. Polyamines have been implicated in protein aggregation which may lead to neuropathic and non neuropathic amyloidosis. Change in the level of polyamine concentration has been associated with ageing and neurodegeneration such as Parkinson's disease, Alzheimer's disease. Lysozyme aggregation in the presence of polyamines leads to non neuropathic amyloidosis. Polyamine analogues can suppress or inhibit protein aggregation suggesting their efficacy against amyloidogenic protein aggregates. In this study we report the comparative interactions of lysozyme with the polyamine analogue, 1-naphthyl acetyl spermine in comparison with the biogenic polyamines through spectroscopy, calorimetry, imaging and docking techniques. The findings revealed that the affinity of binding varied as spermidine > 1-naphthyl acetyl spermine > spermine. The biogenic polyamines accelerated the rate of fibrillation significantly, whereas the analogue inhibited the rate of fibrillation to a considerable extent. The polyamines bind near the catalytic diad residues viz. Glu35 and Asp52, and in close proximity of Trp62 residue. However, the analogue showed dual nature of interaction where its alkyl amine region bind in same way as the biogenic polyamines bind to the catalytic site, while the naphthyl group makes hydrophobic contacts with Trp62 and Trp63, thereby suggesting its direct influence on fibrillation. This study, thus, potentiates, the development of a polyamine analogue that can perform as an effective inhibitor targeted towards aggregation of amyloidogenic proteins.
Sections du résumé
BACKGROUND
Polyamines can induce protein aggregation that can be related to the physiology of the cellular function. Polyamines have been implicated in protein aggregation which may lead to neuropathic and non neuropathic amyloidosis.
SCOPE OF REVIEW
Change in the level of polyamine concentration has been associated with ageing and neurodegeneration such as Parkinson's disease, Alzheimer's disease. Lysozyme aggregation in the presence of polyamines leads to non neuropathic amyloidosis. Polyamine analogues can suppress or inhibit protein aggregation suggesting their efficacy against amyloidogenic protein aggregates.
MAJOR CONCLUSIONS
In this study we report the comparative interactions of lysozyme with the polyamine analogue, 1-naphthyl acetyl spermine in comparison with the biogenic polyamines through spectroscopy, calorimetry, imaging and docking techniques. The findings revealed that the affinity of binding varied as spermidine > 1-naphthyl acetyl spermine > spermine. The biogenic polyamines accelerated the rate of fibrillation significantly, whereas the analogue inhibited the rate of fibrillation to a considerable extent. The polyamines bind near the catalytic diad residues viz. Glu35 and Asp52, and in close proximity of Trp62 residue. However, the analogue showed dual nature of interaction where its alkyl amine region bind in same way as the biogenic polyamines bind to the catalytic site, while the naphthyl group makes hydrophobic contacts with Trp62 and Trp63, thereby suggesting its direct influence on fibrillation.
GENERAL SIGNIFICANCE
This study, thus, potentiates, the development of a polyamine analogue that can perform as an effective inhibitor targeted towards aggregation of amyloidogenic proteins.
Identifiants
pubmed: 32045632
pii: S0304-4165(20)30047-7
doi: 10.1016/j.bbagen.2020.129557
pii:
doi:
Substances chimiques
Amyloid
0
Avian Proteins
0
Biogenic Polyamines
0
Protein Aggregates
0
1-naphthylacetylspermine
122306-11-0
Spermine
2FZ7Y3VOQX
Muramidase
EC 3.2.1.17
Spermidine
U87FK77H25
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
129557Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.