Binding and stabilization of transthyretin by curcumin

Pullakhandam, Raghu; Srinivas, Pooja; Nair, Madhavan K.; Reddy, G. Bhanuprakash

doi:10.1016/j.abb.2009.02.013

Cited by 54 publications

(65 citation statements)

References 35 publications

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“…Pullakhandam et al observed the phenomenon experimentally. 49 Theoretically, log RP should have a good correlation with E int . However, if only the neutral forms of the compounds are considered, no correlations between log RP and E int (p > 0.05) can be observed.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Anionic Phenolic Compounds Bind Stronger with Transthyretin than Their Neutral Forms: Nonnegligible Mechanisms in Virtual Screening of Endocrine Disrupting Chemicals

Yang

Xie

Chen

et al. 2013

Chem. Res. Toxicol.

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The molecular structures of many endocrine-disrupting chemicals (EDCs) contain groups that ionize under physiological pH conditions. It is unclear whether the neutral and ionic forms have different binding mechanisms with the macromolecular targets. We selected phenolic compounds and human transthyretin (hTTR) as a model system and employed molecular docking with quantum mechanics/molecular mechanics optimizations to probe the mechanisms. The binding patterns of ionizable ligands in hTTR crystal structures were also analyzed. We found that the anionic forms of the phenolic compounds bind stronger than the corresponding neutral forms with hTTR. Electrostatic and van de Waals interactions are the dominant forces for most of the anionic and neutral forms, respectively. Because of the dominant and orientational electrostatic interactions, the -O(-) groups point toward the entry port of the binding site. The aromatic rings of the compounds also form cation-π interactions with the -NH3(+) group of Lys 15 residues in hTTR. Molecular descriptors were selected to characterize the interactions and construct a quantitative structure-activity relationship model on the relative competing potency of chemicals with T4 binding to hTTR. It is concluded that the effects of ionization should not be neglected when constructing in silico models for screening of potential EDCs.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Anionic Phenolic Compounds Bind Stronger with Transthyretin than Their Neutral Forms: Nonnegligible Mechanisms in Virtual Screening of Endocrine Disrupting Chemicals

Yang

Xie

Chen

et al. 2013

Chem. Res. Toxicol.

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“…Curcumin has been previously reported to bind to TTR WT [20]. However, no further characterization of the interaction has been conducted.…”

Section: Discussionmentioning

confidence: 99%

Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation

Ferreira¹,

Saraiva

Almeida³

2011

FEBS Letters

136

126

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Edited by Jesus AvilaKeywords: Transthyretin Amyloid inhibitor Fibril formation (À)-Epigallocatechin-3-gallate Curcumin a b s t r a c t Several natural polyphenols with potent inhibitory effects on amyloid fibril formation have been reported. Herein, we studied modulation of transthyretin (TTR) fibrillogenesis by selected polyphenols. We demonstrate that both curcumin and nordihydroguaiaretic acid (NDGA) bind to TTR and stabilize the TTR tetramer. However, while NDGA slightly reduced TTR aggregation, curcumin strongly suppressed TTR amyloid fibril formation by generating small ''off-pathway'' oligomers and EGCG maintained most of the protein in a non-aggregated soluble form. This indicates alternative mechanisms of action supported by the occurrence of different non-toxic intermediates. Moreover, EGCG and curcumin efficiently disaggregated pre-formed TTR amyloid fibrils. Our studies, together with the safe toxicological profile of these phytochemicals may guide a novel pharmacotherapy for TTR-related amyloidosis targeting different steps in fibrillogenesis. Structured summary of protein interactions:TTR binds to TTR by comigration in gel electrophoresis (View interaction) TTR binds to TTR by dynamic light scattering (View interaction) TTR binds to TTR by electron microscopy (View interaction)

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“…These compounds have a remarkable effect on inhibiting amyloid structure formation, and a possible general effect on the amyloidogenic process of very different proteins. The anti-amyloidogenic effect of curcumin has been previously shown on the Aȕ peptide, alpha-synuclein, prion protein, and transthyretin [189,[192][193][194]. In an experiment on another model protein, namely, insulin, various concentrations (ranging from 2 to 8 micromolars) of curcumin were utilised in physiological conditions (pH 7.5, and 37 °C) and shown to be effective in decreasing fibrillogenesis [130].…”

Section: Polyphenols and Other Antioxidantsmentioning

confidence: 99%

Protein-Protein interactions leading to aggregation: Perspectives on mechanism, significance and control

Ebrahim‐Habibi

Morshedi

Rezaei‐Ghaleh

et al. 2010

JICS

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Protein aggregates, whether amorphous or structured (amyloid), have attracted much attention in recent years and despite extensive efforts, the mechanism of their formation is poorly understood. While "natural" aggregation (polymerization) of monomers could improve the biological function of some proteins, it is usually the darker side of this phenomenon which is discussed in many studies: deleterious aggregation that could lead to loss of biological activity under in vitro conditions or cause misfolding diseases. In this review, protein aggregation has been overviewed, starting from some general concepts involved in its formation, followed by mentioning studies aimed at elucidation of its kinetics and mechanism, or characterization of intermediates that would be aggregation-prone, and finally, reporting some of the studies related to the design of methods that would control the process. Similarly, amyloid aggregates have been defined, and current methods used in their characterization have been briefly described, with an emphasis on in silico studies. Finally, identification and design of such molecules which may be effective in control of this process is discussed.

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Binding and stabilization of transthyretin by curcumin

Cited by 54 publications

References 35 publications

Anionic Phenolic Compounds Bind Stronger with Transthyretin than Their Neutral Forms: Nonnegligible Mechanisms in Virtual Screening of Endocrine Disrupting Chemicals

Anionic Phenolic Compounds Bind Stronger with Transthyretin than Their Neutral Forms: Nonnegligible Mechanisms in Virtual Screening of Endocrine Disrupting Chemicals

Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation

Protein-Protein interactions leading to aggregation: Perspectives on mechanism, significance and control

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