Insights into the selective binding and toxic mechanism of microcystin to catalase

Hu, Yuandong; Liu, Da

doi:10.1016/j.saa.2013.09.078

Cited by 28 publications

(12 citation statements)

References 30 publications

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“…This is because the values observed in fluorescence spectroscopy are usually related to excited state complexes and ITC measures the ground state complexes. The binding constant for catalase-microcystin complex determined fluorimetrically is 6.12×10 4 M −1 [40], which is lower than catalase-EGCG complex. Microcystin binding to catalase was reported to influence its physiological functions and conformation [40].…”

Section: Discussionmentioning

confidence: 74%

“…Inhibition of human cancer cell growth by tea polyphenols has been observed in H1299, H661, HT-29, H441 and breast cancer cell lines at IC 50 values between (20–75 µg/ml) [39]. Catalase is another cellular enzyme whose interaction with microsystin, a cyanotoxin drug, decreases its enzymatic action [40]. Here its inhibition in K562 cancer cells is reported and its relevance in cancer is demonstrated by the suppression of cell viability.…”

Section: Introductionmentioning

confidence: 87%

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Inhibition of Catalase by Tea Catechins in Free and Cellular State: A Biophysical Approach

2014

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Tea flavonoids bind to variety of enzymes and inhibit their activities. In the present study, binding and inhibition of catalase activity by catechins with respect to their structure-affinity relationship has been elucidated. Fluorimetrically determined binding constants for (−)-epigallocatechin gallate (EGCG) and (−)-epicatechin gallate (ECG) with catalase were observed to be 2.27×106 M−1 and 1.66×106 M−1, respectively. Thermodynamic parameters evidence exothermic and spontaneous interaction between catechins and catalase. Major forces of interaction are suggested to be through hydrogen bonding along with electrostatic contributions and conformational changes. Distinct loss of α-helical structure of catalase by interaction with EGCG was captured in circular dichroism (CD) spectra. Gallated catechins demonstrated higher binding constants and inhibition efficacy than non-gallated catechins. EGCG exhibited maximum inhibition of pure catalase. It also inhibited cellular catalase in K562 cancer cells with significant increase in cellular ROS and suppression of cell viability (IC50 54.5 µM). These results decipher the molecular mechanism by which tea catechins interact with catalase and highlight the potential of gallated catechin like EGCG as an anticancer drug. EGCG may have other non-specific targets in the cell, but its anticancer property is mainly defined by ROS accumulation due to catalase inhibition.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 87%

Inhibition of Catalase by Tea Catechins in Free and Cellular State: A Biophysical Approach

2014

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“…MC-LR also markedly enhanced the •O 2 -and H 2 O 2 formation in primary cultured rat hepatocytes [65,66]. Recently, it's shown that MC-LR can bind to CAT to form a complex and lead to conformational and microenvironmental changes of the protein, which may affect its physiological functions and induce oxidative stress [67].…”

Section: Oxidative Stressmentioning

confidence: 96%

Mechanisms of Microcystin-induced Cytotoxicity and Apoptosis

Chen¹,

Xie

2016

MRMC

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Abstract:In recent years, cyanobacterial blooms have dramatically increased and become an ecological disaster worldwide. Cyanobacteria are also known to produce a wide variety of toxic secondary metabolites, i.e. cyanotoxins. Microcystins (MCs), a group of cyclic heptapeptides, are considered to be one of the most common and dangerous cyanobacterial toxins. MCs can be incorporated into the cells via organic anion transporting polypeptides (Oatps). It's widely accepted that inhibition of protein phosphatases (PPs) and induction of oxidative stress are the main toxic mechanisms of MCs. MCs are able to induce a variety of toxic cellular effects, including DNA damage, cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) disturbance and cell cycle deregulation, all of which can contribute to apoptosis/programmed cell death. This review aimed to summarize the increasing data regarding the intracellular biochemical and molecular mechanisms of MC-induced toxicity and cell death.

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“…However, in the present study, for such a compound in the early stages of development, BSA was employed as a model representing the serum albumins family. Several earlier studies have utilized spectroscopic techniques, particularly fluorescence spectral determination, to explore the different aspects of protein binding to various ligands [34][35][36]. Fluorescence quenching shows decline protein intrinsic fluorescence occurring through diverse molecular interactions [37,38].…”

Section: Fluorescence Spectroscopic Investigation Of the Binding Mechmentioning

confidence: 99%

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

et al. 2017

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As part of the research endeavors to combat cancer, a non-symmetric bis-isatin derivative (compound 3) was synthesized and showed a significant anti-proliferative potency. The current study provides a comprehensive characterization of the interaction of compound 3 with the drug-transporting protein bovine serum albumin (BSA) via the use of spectroscopic tools along with molecular docking studies. Fluorescence spectral measurements showed that the BSA intrinsic fluorescence can be significantly quenched by the addition of compound 3 and the formation of a non-fluorescent complex. Further measurements revealed a static type of quenching with Stern-Volmer and Linweaver-Burk constants of 10 5 . The thermodynamic parameters of the binding were calculated to be ∆S • 105.09 ± 5.32 with ∆H • of −0.72 ± 0.71 and negative ∆G • values. In addition, synchronous fluorescence and 3D fluorescence spectroscopy suggested that compound 3 did not induce conformational changes in BSA. Site competition experiments revealed that compound 3 competes with warfarin within the BSA binding domain (Sudlow site I). This was further confirmed by the molecular docking results showing a binding energy of −25.93 kJ/mol for compound 3-BSA. Hence, the observed results in the present study assumed that the compound 3-BSA binding is spontaneous, involving electrostatic forces and hydrogen bonding.

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Insights into the selective binding and toxic mechanism of microcystin to catalase

Cited by 28 publications

References 30 publications

Inhibition of Catalase by Tea Catechins in Free and Cellular State: A Biophysical Approach

Inhibition of Catalase by Tea Catechins in Free and Cellular State: A Biophysical Approach

Mechanisms of Microcystin-induced Cytotoxicity and Apoptosis

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

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