His18 promotes reactive oxidative stress production in copper-ion mediated human islet amyloid polypeptide aggregation

Huo, Gengyang; Chen, Wenyong; Wang, Jianhua; Chu, Xinxing; Xu, Wei; Li, Bin; Zhang, Yi; Xu, Binqian; Zhou, Xingfei

doi:10.1039/c9ra09943c

Cited by 9 publications

(10 citation statements)

References 41 publications

(200 reference statements)

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“…The strong binding affinity (−6.29 kcal/mol) of ANFLVH with His18 of hIAPP results in the blocking of interactions mediated by His18 in promoting hIAPP aggregation. These results are consistent with earlier studies, which highlighted the key role of His18 in hIAPP amyloid formation [59] as well as in the promotion of reactive oxidative stress in the copper‐ion mediated hIAPP aggregation [60] . Wei et al.…”

Section: Resultssupporting

confidence: 92%

“…These results are consistent with earlier studies, which highlighted the key role of His18 in hIAPP amyloid formation [59] as well as in the promotion of reactive oxidative stress in the copper-ion mediated hIAPP aggregation. [60] Wei et al highlighted that polyphenol resveratrol displayed strong binding with His18 of hIAPP and inhibited its oligomerization and amyloid formation, which is consistent with the observation that His18 is crucial for on-pathway oligomer formation by hIAPP. [61]…”

Section: Binding Free Energy Analysis Between Hiapp and Anflvhsupporting

confidence: 55%

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Deciphering the Inhibitory Mechanism of hIAPP‐Derived Fragment Peptide Against hIAPP Aggregation in Type 2 Diabetes**

Kaur

Goyal

2020

ChemistrySelect

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The aggregates of human islet amyloid polypeptide (hIAPP or amylin) are well-known causative agents of type 2 diabetes (T2D). Previous experimental studies reported that hexapeptide ANFLVH inhibited IAPP aggregation and completely prevented IAPP-mediated toxicity. However, the underlying inhibitory mechanism at the atomic level is not completely understood. In this regard, the molecular mechanism of the inhibition of hIAPP aggregation in the presence of ANFLVH has been elucidated by molecular dynamics (MD) simulations in the present study. MD simulation analysis highlighted that ANFLVH prevented the conformational transition of hIAPP by stabilizing the native helical conformation. The binding free energy analysis by the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method highlighted favourable binding (ΔG binding = À 49.90 � 0.67 kcal/mol) of ANFLVH with hIAPP and depicted a significant contribution of the van der Waals interaction term (ΔE vdW = À 46.33 � 0.32 kcal/mol) in the stability of the hIAPP-ANFLVH complex. The per-residue binding free energy highlighted that ANFLVH strongly interacted with His18 of hIAPP, which has been reported as a key residue in mediating the hIAPP self-assembly process. The present work sheds light on the inhibitory mechanism of ANFLVH against hIAPP aggregation at the atomic level. The study will guide the rational design and development of therapeutic candidates against hIAPP aggregation in T2D.

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Section: Resultssupporting

confidence: 92%

Section: Binding Free Energy Analysis Between Hiapp and Anflvhsupporting

confidence: 55%

Deciphering the Inhibitory Mechanism of hIAPP‐Derived Fragment Peptide Against hIAPP Aggregation in Type 2 Diabetes**

Kaur

Goyal

2020

ChemistrySelect

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“…In a contradiction, some reports state that the Cu(II)-hIAPP complexes yield H 2 O 2 to a reduced amount compared to that by free Cu(II) in solution, suggestive of a possible sacrificial protecting role for hIAPP cohabited with Cu(II) in higher concentration. , However, His18 of hIAPP as one of the Cu(II) anchoring residue is established to have the critical role in stimulating H 2 O 2 production during hIAPP aggregation. This is probably for the reason that the donation of electrons from hIAPP (specifically His18) to Cu(II) can form the redox-active metal–peptide complexes, that in turn can encourage the H 2 O 2 formation …”

Section: Type 2 Diabetes Mellitus (T2dm)mentioning

confidence: 99%

Second Sphere Interactions in Amyloidogenic Diseases

et al. 2022

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Amyloids are protein aggregates bearing a highly ordered cross β structural motif, which may be functional but are mostly pathogenic. Their formation, deposition in tissues and consequent organ dysfunction is the central event in amyloidogenic diseases. Such protein aggregation may be brought about by conformational changes, and much attention has been directed toward factors like metal binding, post-translational modifications, mutations of protein etc., which eventually affect the reactivity and cytotoxicity of the associated proteins. Over the past decade, a global effort from different groups working on these misfolded/unfolded proteins/peptides has revealed that the amino acid residues in the second coordination sphere of the active sites of amyloidogenic proteins/peptides cause changes in H-bonding pattern or protein–protein interactions, which dramatically alter the structure and reactivity of these proteins/peptides. These second sphere effects not only determine the binding of transition metals and cofactors, which define the pathology of some of these diseases, but also change the mechanism of redox reactions catalyzed by these proteins/peptides and form the basis of oxidative damage associated with these amyloidogenic diseases. The present review seeks to discuss such second sphere modifications and their ramifications in the etiopathology of some representative amyloidogenic diseases like Alzheimer’s disease (AD), type 2 diabetes mellitus (T2Dm), Parkinson’s disease (PD), Huntington’s disease (HD), and prion diseases.

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“…It can be confirmed in a study conducted by Tomita et al (19)on the pancreas of type 2 diabetic patients. The mechanism of action of hIAPP is similar to glucolipotoxicity: increased expression of hIAPP disrupts autophagy and the ubiquitin-protease system (20), triggers stress pathways, thus leading to apoptosis (21).…”

Section: Glucotoxicity or Glucolipotoxicity And Islet Amyloid Polypep...mentioning

confidence: 99%

Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus

et al. 2022

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Type 2 diabetes mellitus(T2DM) is regarded as one of the most severe chronic metabolic diseases worldwide, which poses a great threat to human safety and health. The main feature of T2DM is the deterioration of pancreatic beta-cell function. More and more studies have shown that the decline of pancreatic beta-cell function in T2DM can be attributable to beta-cell apoptosis, but the exact mechanisms of beta-cell apoptosis in T2DM are not yet fully clarified. Therefore, in this review, we will focus on the current status and progress of research on the mechanism of pancreatic beta-cell apoptosis in T2DM, to provide new ideas for T2DM treatment strategies.

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His18 promotes reactive oxidative stress production in copper-ion mediated human islet amyloid polypeptide aggregation

Abstract: His18 promotes H2O2 production in copper-ion mediated hIAPP aggregation.

Cited by 9 publications

References 41 publications

Deciphering the Inhibitory Mechanism of hIAPP‐Derived Fragment Peptide Against hIAPP Aggregation in Type 2 Diabetes**

Deciphering the Inhibitory Mechanism of hIAPP‐Derived Fragment Peptide Against hIAPP Aggregation in Type 2 Diabetes**

Second Sphere Interactions in Amyloidogenic Diseases

Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus

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