Dihydro-alpha-lipoic acid binds to human serum albumin at Sudlow I binding site

ABSTRACTBinding of dihydro-alpha-lipoic acid (DHLA) to human serum albumin (HSA) was characterised in detail in this study. Binding process was monitored by spectroscopic methods and molecular docking approach. HSA binds DHLA with moderate affinity, 0.80 ± 0.007 × 104 M−1. Spectroscopic data demonstrated that the preferential binding site for DHLA on HSA is IIA (Sudlow I). Hydrogen bonds and electrostatic interactions were identified as the key binding interactions. DHLA binding thermally stabilized HSA, yet it had no effect on HSA structure and its susceptibility to trypsin digestion. Molecular docking confirmed that Sudlow I site accommodated DHLA in a certain conformation in order for binding to occur. Molecular dynamic simulation showed that formed complex is stable. Reported results offer future perspectives for investigations regarding the use of DHLA as a dietary intervention but also raise concerns about the effectiveness of alpha-lipoic acid and DHLA in treatment of patients with COVID-19.

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Physicochemical characterisation of dihydro-alpha-lipoic acid interaction with human serum albumin by multi-spectroscopic and molecular modelling approach

Journal of the Serbian Chemical Society ◽

10.2298/jsc210420041g ◽

2021 ◽

pp. 41-41

Author(s):

Nikola Gligorijevic ◽

Vladimir Sukalovic ◽

Simeon Minic ◽

Goran Miljus ◽

Olgica Nedic ◽

...

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Lipoic Acid ◽

Food Supplement ◽

Alpha Lipoic Acid ◽

Salt Bridges ◽

Preferential Binding ◽

Docking Approach

The binding of popular food supplement and a well-known anti-oxidant, dihydro-alpha-lipoic acid (DHLA) to human serum albumin (HSA) was characterised. The binding was monitored by several spectroscopic methods together with molecular docking approach. HSA was able to bind DHLA with moderate affinity, 1.00?0.05?104 M-1. Spectroscopic data demonstrated that the preferential binding site for DHLA on HSA is IIA (Sudlow I). Both experimental and molecular docking analysis identified electrostatic (salt bridges) and hydrogen bonds as the key interactions involved in DHLA binding to HSA. Molecular docking confirmed that Sudlow I site could accommodate DHLA and ligand is bound to the protein in a specific conformation. The molecular dynamic simulation showed that the formed complex is stable. Binding of DHLA does not affect the structure of protein, but it thermally stabilises HSA. Bound DHLA had no effect on the susceptibility of HSA to trypsin digestion. Since DHLA is a commonly used food supplement, the knowledge of its pharmacokinetics and pharmacodynamic properties in an organism is very important. This study further expands it by providing a detailed analysis of its interaction with HSA, the primary drug transporter in the circulation.

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Probing the toxic interactions between the reactive dye Drimaren Red and Human Serum Albumin

10.1101/2021.07.17.452798 ◽

2021 ◽

Author(s):

Thais Meira Menezes ◽

Caio Rodrigo Dias de Assis ◽

Antonio Marinho da Silva Neto ◽

Priscila Gubert ◽

Marcos Gomes Ghislandi ◽

...

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Textile Industry ◽

Electrostatic Interactions ◽

Reactive Dye ◽

Biological Macromolecules ◽

Spectroscopic Techniques ◽

Binding Characteristics

Azo dyes like Drimaren Red CL-5B (DR, CI Reactive Red 241) represent a class of compounds extensively used in the textile industry and are extremely dangerous to the environment and human health. Therefore, understanding the binding characteristics between such substances and biological macromolecules is essential from a toxic-kinetic perspective. The molecular interaction between DR and Human Serum Albumin (HSA) was investigated through spectroscopic techniques and molecular docking approaches. The results indicate that DR quenches HSA fluorescence following a static mechanism (corroborated by UV-Vis studies) with a moderate interaction (Ka~105 M-1), guided by electrostatic interactions (DS> 0 and DH< 0). DR is 5.52 nm distant from fluorophore residue Trp-214 (according to FRET investigations), and the interaction is mainly related to Tyr residues (as revealed by synchronous fluorescence). The Ellman assay identified a decrease in the content of HSA free thiol. The results of the RLS demonstrate that there are HSA alterations, suggesting damage to the confirmation of the protein. Molecular docking suggests the binding site of DR was located in subdomain IIB HSA, corroborating the experimental properties. Finally, the results suggest a high potential for DR toxicity triggered by contact with key proteins, which affects the biomolecule functionalities.

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Redox Homeostasis of Albumin in Relation to Alpha-Lipoic Acid and Dihydrolipoic Acid

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.3.3.11786 ◽

2010 ◽

Vol 3 (3) ◽

pp. 206-213 ◽

Cited By ~ 19

Author(s):

Pinar Atukeren ◽

Seval Aydin ◽

Ezel Uslu ◽

MKoray Gumustas ◽

Ufuk Cakatay

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Lipoic Acid ◽

Protein Oxidation ◽

Antioxidant Properties ◽

Oxidative Modification ◽

Breakdown Product ◽

Alpha Lipoic Acid ◽

Dihydrolipoic Acid

Albumin represents the predominant circulating antioxidant agent in plasma exposed to continuous oxidative stress and a change in serum albumin structure accounts for its antioxidant properties. Alterations in the redox status of albumin may result in impairments of its biological properties. Alpha-lipoic acid (LA), a naturally occurring thiol compound found in virtually all species, is a potent antioxidant with high efficacy which is also involved in the chelation of metal ions, regeneration of antioxidants, and repair of oxidatively damaged proteins. In human body LA is rapidly reduced to dihydrolipoic acid (DHLA) after intake into the cell. Both, LA and DHLA are amphipathic molecules which act as antioxidants both in hydrophilic and lipophilic environments. The present study aimed to investigate the antioxidant/pro-oxidant effects of LA and DHLA due to their concentrations in metal-catalyzed protein oxidation (MCO) of human serum albumin (HSA). Progressive oxidative modification of albumin was found in MCO system by an increased content of protein hydroperoxides (POOH), protein carbonyl groups (PCO) which is the former's major breakdown product, and other protein oxidation markers such as advanced oxidized protein products (AOPP) and protein thiol groups (P-SH). The possible antioxidant protective effects of LA and DHLA were observed with 25 µM and 50 µM; DHLA being more influential. Protein oxidation parameters were found to be lower and P-SH levels seemed higher. However, prooxidant effects of both LA and DHLA came on the scene with increased concentrations of 75 µM and 100 µM where the latter seemed the most hazardous with contradicted results. It is clear that the loss of biological activity of human serum albumin by MCO system appears of medical relevance and if LA exerts similar effects seen in the present study, it is possible that cellular prooxidant activity can also result consuming this unique antioxidant in certain doses.

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Synthesis, characterization, in vitro cytotoxicity, in silico ADMET analysis and interaction studies of 5-dithiocarbamato-1,3,4-thiadiazole-2-thiol and its zinc(ii) complex with human serum albumin: combined spectroscopy and molecular docking investigations

RSC Advances ◽

10.1039/c6ra17322e ◽

2016 ◽

Vol 6 (108) ◽

pp. 106516-106526 ◽

Cited By ~ 21

Author(s):

Fereshteh Shiri ◽

Somaye Shahraki ◽

Sadegh Baneshi ◽

Massoud Nejati-Yazdinejad ◽

Mostafa Heidari Majd

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Binding Site ◽

In Silico ◽

In Vitro Cytotoxicity ◽

Interaction Studies ◽

In Silico Admet

The binding site of new complex Zn(ii) of 5-dithiocarbamato-1,3,4-thiadiazole-2-thiol and HAS.

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Targeting the Nalidixic Acid Binding Site on Human Serum Albumin Through Computational Approach: A Re-Investigation

Biointerface Research in Applied Chemistry ◽

10.33263/briac122.15201525 ◽

2021 ◽

Vol 12 (2) ◽

pp. 1520-1525

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Binding Site ◽

Nalidixic Acid ◽

Dna Supercoiling ◽

Serum Albumins ◽

Binding Preference ◽

Tract Infections

Nalidixic acid (NA) is a quinolone drug used to treat urinary tract infections. It inhibits bacterial gyrase-DNA complex formation, an essential step for DNA supercoiling during bacterial replication. Due to the medical application of this drug, it would be interesting to get insight into its binding mechanism with human serum albumin (HSA), the primary carrier protein in blood circulation. Two reports of NA binding to HSA were published using molecular docking approaches. The first report revealed that the preferred binding site of NA was Site II of serum albumins, while the recent finding predicted Site I of bovine serum albumin (BSA) as the preferred site. Given the high sequence homology between these albumins, it is presumed that the binding preference of this drug should be the same in these proteins. To re-investigate this phenomenon, the interaction of NA with HSA was conducted using AutoDockTool 4.0. The molecular docking results revealed that NA binding preference was at Site I, involving Lys 199 in HSA, due to the formation of more significant contacts. Hence, it is concluded that any variable or parameters in the software should be wisely standardized to minimize the controversial results using different programs.

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