In-silico Investigation of the Interaction between Beta-class Glutathione S-Transferase and Five Antibiotics, namely; Ampicillin, Tetracycline, Chloramphenicol, Ciprofloxacin and Cephalexin

Glutathione s-transferases(GSTs) are enzymes involved in the conjugation and deactivation of various xenobiotics including drugs. Thisin-silico study was undertaken in order to investigate the interaction between beta-class glutathione s-transferase and five selected antibiotics, namely; ampicillin, tetracycline, chloramphenicol, ciprofloxacin and cephalexin using molecular docking study. RaptorX server was used to predict the amino acids involved at the binding sitewhile molecular docking study was employed in order to investigate the binding interactions.RaptorX predicted several amino acids which were different from the ones observed in molecular docking because of the variability in the substrate binding site of GSTs however, all the amino acids predicted by RaptorX were also found to be involved in the GSH binding.Lys107, Phe109, Ser110, Leu113, Trp114, His115 and Arg123, Leu168 were the amino acids involved in the binding of various antibiotics to the substrate binding site of the protein while Ala9, Cys10, Leu32, Tyr51, Val52, Pro53, Glu65 and Ala66were involved in the binding of the co-substrate GSH to the binding site of the protein. The results indicated that all the antibiotics showed a good binding affinity with the beta class GST and are therefore capable of deactivating the drugs. With these, finding a beta class GST inhibitors alongside antibiotics during a treatment of diseases will be of beneficial in the current fight against antibiotic resistance.

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Dehalogenation of Dichlorobenzoates by Acidovorax sp. KKS102’s beta class Glutathione S-transferase and its Mutants

UMYU Journal of Microbiology Research (UJMR) ◽

10.47430/ujmr.2161.009 ◽

2021 ◽

Vol 6 (1) ◽

pp. 70-76

Author(s):

D. Shehu ◽

◽

Zazali Alias

Keyword(s):

Molecular Docking ◽

Chloride Ion ◽

Docking Study ◽

Wild Type ◽

Glutathione S Transferase ◽

Molecular Docking Study ◽

E Coli ◽

Detection Assay ◽

Glutathione S Transferases ◽

The One

Glutathione s-transferases (GSTs) are ubiquitous family of enzymes well known for their detoxification function. Several different classes of the enzyme exist with beta class being the one specific to bacteria. Recently, the enzymes were found to exhibit other functions, in particular dehalogenation of some organic compounds. This property could be extremely useful especially in the bioremediation of some organochlorine pollutants. A beta class GST from Acidovorax sp. KKS102 designated as KKS-BphK was previously cloned and characterized. In this research, molecular docking study was first employed to investigate the possibility of binding of the protein to dichlorobenzoates; byproducts of polychlorobiphenyl degradation. The wild type enzyme together with other mutants were expressed using E. coli BL21 (DE3) cells and purified. The dehalogenation function of the enzymes against dichlorobenzoate derivatives was also investigated through chloride ion detection assay. The results of the molecular docking study indicated the possibility of binding of KKS-BphK to these substrates. Both the wild type and the mutants showed dehalogenation function against the model substrate 1-chloro-2,4- dinitrobenzene (CDNB). Furthermore, the enzymes also showed dehalogenation function against 2,4-dichlorobenzoate derivatives. However, in testing the activity of the enzymes toward 2,5- dichlorobenoate and 2,6-dichlorobenzoate, only K107T and A180P mutants showed some activity while the wild type and C10F mutant showed zero activity. The research indicates the usefulness of beta class GST in the dehalogenation of dichlorobenzoates in addition to their known function of dehalogenating monochlorobenzoates. Keywords: Glutathione s-transferase, Mutants, Beta class, dehalogenation, dichlorobenzoates.

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BETWEEN ARTEMISININ AND DERIVATIVES WITH NEURAMINIDASE: A DOCKING STUDY INSIGHT

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i8.18667 ◽

2017 ◽

Vol 10 (8) ◽

pp. 304 ◽

Cited By ~ 2

Author(s):

Mohammad Rizki Fadhil Pratama ◽

Tutus Gusdinar

Keyword(s):

Amino Acids ◽

Molecular Docking ◽

Docking Study ◽

Basis Sets ◽

Molecular Docking Study ◽

Oseltamivir Resistance ◽

Hartree Fock ◽

In Silico Molecular Docking ◽

Free Energy Of Binding ◽

The Relationship

Objectives: This study aims to find the relationship between artemisinins and neuraminidase (NA) with molecular docking study and also to determine the most potent NA inhibitor from artemisinin and derivatives.Methods: All ligands were sketched and optimized using Gaussian 03W with Hartree-Fock method basis sets 6-311G. Molecular docking was performed using AutoDock 4.2.3 toward NA in complexes with oseltamivir as co-crystal ligand. The main parameters used were the free energy of binding (ΔG) and dissociation constant (Ki) as affinity marker.Results: Artesunate provided most negative free ΔG and lowest Ki toward NA with −9.55 kcal/mol and 100.66 nM, respectively. Artesunate shows higher affinity than oseltamivir with interactions between artesunate and amino acids at position 246 had important influences on artesunate affinity toward NA from H5N1.Conclusion: In silico molecular docking results indicated that artesunate could be considered as NA inhibitor and should be potential to be developed as anti-influenza particularly to H5N1 with oseltamivir resistance.

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Effects of Substrate-Binding Site Residues on the Biochemical Properties of a Tau Class Glutathione S-Transferase from Oryza sativa

Genes ◽

10.3390/genes11010025 ◽

2019 ◽

Vol 11 (1) ◽

pp. 25 ◽

Cited By ~ 2

Author(s):

Xue Yang ◽

Jinchi Wei ◽

Zhihai Wu ◽

Jie Gao

Keyword(s):

Amino Acids ◽

Enzyme Activity ◽

Abiotic Stress ◽

Binding Site ◽

Stress Responses ◽

Stress Resistance ◽

Substrate Binding ◽

Biochemical Properties ◽

Biotic And Abiotic Stress ◽

Substrate Binding Site

Glutathione S-transferases (GSTs)—an especially plant-specific tau class of GSTs—are key enzymes involved in biotic and abiotic stress responses. To improve the stress resistance of crops via the genetic modification of GSTs, we predicted the amino acids present in the GSH binding site (G-site) and hydrophobic substrate-binding site (H-site) of OsGSTU17, a tau class GST in rice. We then examined the enzyme activity, substrate specificity, enzyme kinetics and thermodynamic stability of the mutant enzymes. Our results showed that the hydrogen bonds between Lys42, Val56, Glu68, and Ser69 of the G-site and glutathione were essential for enzyme activity and thermal stability. The hydrophobic side chains of amino acids of the H-site contributed to enzyme activity toward 4-nitrobenzyl chloride but had an inhibitory effect on enzyme activity toward 1-chloro-2,4-dinitrobenzene and cumene hydroperoxide. Different amino acids of the H-site had different effects on enzyme activity toward a different substrate, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. Moreover, Leu112 and Phe162 were found to inhibit the catalytic efficiency of OsGSTU17 to 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, while Pro16, Leu112, and Trp165 contributed to structural stability. The results of this research enhance the understanding of the relationship between the structure and function of tau class GSTs to improve the abiotic stress resistance of crops.

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Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

BioMed Research International ◽

10.1155/2014/291214 ◽

2014 ◽

Vol 2014 ◽

pp. 1-21 ◽

Cited By ~ 17

Author(s):

Shikhar Gupta ◽

C. Gopi Mohan

Keyword(s):

Molecular Docking ◽

Binding Site ◽

Enzyme Inhibitors ◽

Acetylcholinesterase Inhibitors ◽

Docking Study ◽

Molecular Docking Study ◽

Test Set ◽

Zinc Database ◽

Pharmacophore Hypotheses ◽

Pharmacophore Models

In this study, we have employedin silicomethodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

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N‐Linoleyl amino acids as chiral probes for the substrate binding site of soybean lipoxygenase‐1

The FASEB Journal ◽

10.1096/fasebj.21.5.a276-d ◽

2007 ◽

Vol 21 (5) ◽

Author(s):

Charles H. Clapp ◽

Justin Pachuski ◽

Kathleen A. Bishop ◽

Megan M. Young

Keyword(s):

Amino Acids ◽

Binding Site ◽

Substrate Binding ◽

Soybean Lipoxygenase ◽

Substrate Binding Site

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Structure and Function of the Xenobiotic Substrate Binding Site of a Glutathione S-Transferase as Revealed by X-ray Crystallographic Analysis of Product Complexes with the Diastereomers of 9-(S-Glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene

Biochemistry ◽

10.1021/bi00171a002 ◽

1994 ◽

Vol 33 (5) ◽

pp. 1043-1052 ◽

Cited By ~ 73

Author(s):

Xinhua Ji ◽

William W. Johnson ◽

Muctarr A. Sesay ◽

Laura Dickert ◽

Satya M. Prasad ◽

...

Keyword(s):

Binding Site ◽

Substrate Binding ◽

Crystallographic Analysis ◽

Structure And Function ◽

Glutathione S Transferase ◽

Substrate Binding Site ◽

X Ray ◽

And Function

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Molecular Docking Studies of α-Pyrone Derivatives Isolated from Alternaria phragmospora as CRM1 Inhibitors

10.20944/preprints202009.0689.v1 ◽

2020 ◽

Author(s):

Ahmed Metwaly ◽

Ibrahim Eissa ◽

Ahmad Mostafa

Keyword(s):

Amino Acids ◽

Molecular Docking ◽

Chromosome Region ◽

Docking Study ◽

Docking Studies ◽

Molecular Docking Study ◽

Chemically Modified ◽

Structure Activity ◽

Modes Of Interaction ◽

Chromosome Region Maintenance

Some α-Pyrone derivatives isolated from Alternaria phragmospora fungus showed promising anti leukemic activities, while others were inactive. CRM1/XPO1 (chromosome region maintenance 1 protein, also called exportin1 or PO1 in humans) has been chosen as a target for antileukemic molecular docking study for those compounds to understand their modes of interaction and structure activity relationships. The results showed that two (2 and 4), out of six, natural α-Pyrone derivatives exhibited well-established interactions with the amino acids of the receptor, which was in agreement with the experimental anti-leukemic results of these compounds. Moreover, twenty hypothetical chemically modified α-Pyrone derivatives (7-27) have been designed. Compounds 7, 8, 22 and 24 showed more efficient docking properties than the previously considered natural compounds.

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Molecular Docking Analysis of Chloroquine and Hydroxychloroquine and Design of Anti-SARS-CoV2 Protease Inhibitor

Modern Applied Science ◽

10.5539/mas.v14n10p52 ◽

2020 ◽

Vol 14 (10) ◽

pp. 52

Author(s):

Usman Abdulfatai ◽

Adamu Uzairu ◽

Gideon Adamu Shallangwa ◽

Sani Uba

Keyword(s):

Amino Acids ◽

Molecular Docking ◽

Binding Energy ◽

Binding Site ◽

Docking Simulation ◽

Binding Energies ◽

Drug Candidate ◽

Molecular Docking Study ◽

Docking Analysis ◽

Molecular Docking Analysis

In this present investigation, simulated molecular docking study of chloroquine and hydroxychloroquine compounds were investigated on the SARS-CoV2 enzyme to determine the types of amino acids responsible for the biochemical reaction at the binding site. A structure-based docking design technique was explored in designing a novel derivative of chloroquine for the treatment and management of new COVID 19 disease. To achieve this, the molecular docking simulation method was used to investigate the level of chloroquine and hydroxychloroquine (Drugs presently under clinical trial) interactions on SARS-CoV2 enzyme (a causative agent of COVID 19 disease). Chloroquine and hydroxychloroquine which has been debated as drugs for the management of COVID 19 were subjected to molecular docking analysis, and the binding energies generated were found to be -6.1 kcal/mol and -6.8 kcal/mol respectively. Moreover, novel 2-((4-((7-chloroquinolin-4 yl) amino)pentyl)((methylamino)methyl)amino) ethan-1-ol as an anti-SARS-CoV2 protease was designed through the structural modification of hydroxychloroquine. The binding energy of this drug candidate was found to be -6.9 kcal/mol. This novel drug was found to formed hydrogen and conventional interactions with the binding site of SARS-CoV2 protease through amino acids such as Glutamic acid (GLU166), Glycine (GLY143), Phenylalanine (PHE140), Asparagine (ASN142), Histidine (HIS163), His (HIS172, HIS41, HIS163), Leucine (LEU41, LEU27), Glycine (GLY143), Glutamine (GLN189), Methionine (MET49, MET165), Serine (SER 46), Cysteine (CYS145) and Threonine (THR25). With this binding energy, this new drug candidate could bind better to the human SARS-CoV2 protease’ binding site. This research provides a clue for other scientists on various ways of designing and identify the types of amino acids that may be responsible for biochemical action on SARS-CoV2 protease.

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