scholarly journals Exploring the action of new FimH inhibitors against CTX– 15 enzyme by enzoinformatics approach: A plausible arsenal against drug-resistant uropathogenic bacterial strains

2021 ◽  
Vol 20 (11) ◽  
pp. 2363-2370
Author(s):  
Amir Saeed ◽  
Khalid Alshaghdali ◽  
Mohd Saeed ◽  
Mousa Alreshidi
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Active Site ◽  
Treatment Options ◽  
Positive Control ◽  
Drug Resistant ◽  
Amino Acid Residues ◽  
Bacterial Strains ◽  
Docking Approach ◽  
Uropathogenic Bacteria

Purpose: To explore the potency of FimH inhibitors against CTX-M β-lactamase enzyme type 15, in view of the increasing prevalence of CTX-M 15 in uropathogenic strains which has reduced the treatment options to minimal.Method: FimH inhibitors were targeted against CTXM-15 by a molecular docking approach. Thereafter, the best ligand-target confirmation was selected and analyzed using LIGPLOT+ Version v.2.1. The hydrophobic and hydrogen bonding among the catalytic site amino acids of CTXM-15 and the FimH inhibitors were analyzed and 3-D structures were converted into 2-D images by LIGPLOT algorithm.Results: Out of all the FimH inhibitors tested, 3′-chloro-4′- (α-D-mannopyranosyloxy) biphenyl-4- carbonitrile, para-biphenyl-2-methyl-3′-methylamidemannoside, para-biphenyl-2-methyl-3′,5′dimethylamide-α-D-mannoside, and thiazolylamino mannoside exhibited better interaction with the CTX-M15 active site than the positive control avibactam. Moreover, in CTX-M 15, the amino acid residues, Ser70, Tyr105, Ser130, Asn132, Thr216, Thr235, Gly236, and Ser237 were commonly interacting with these FimH inhibitors as well as avibactam.Conclusion: The predicted findings suggest that these FimH inhibitors could be explored as potential CTX-M 15 inhibitors to cope-up with resistance issues of uropathogenic bacteria in the form of an alternate strategy.

scholarly journals Evaluation of Seaweed Sulfated Polysaccharides As Natural Antagonists Targeting Salmonella typhi OmpF: Molecular Docking and Pharmacokinetic Profiling

2021 ◽  
Author(s):  
ARUN KUMAR MALAISAMY ◽  
Mahalakshmi Murugan ◽  
Ashok Kumar Vairamuthu ◽  
Manikka Kubendran Aravind ◽  
Sathaiah Gunaseelan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Pathogenic Bacteria ◽  
Biological Activities ◽  
Salmonella Typhi ◽  
Sulfated Polysaccharides ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Microbial Diseases ◽  
Wide Range ◽  
Docking Approach

Abstract Background: Salmonella belongs to the Enterobacteriaceae family, a gram-negative, non-spore-forming, rod-shaped, motile, and pathogenic bacteria that transmit through unhygienic conditions. It is estimated that 21 million new infections arise every year, resulting in approximately 200,000 deaths. It is more prevalent among children, the old aged, and immunocompromised individuals. The frequent usage of classical antimicrobials has begun the increasing emergence of various drug-resistant pathogenic bacterial strains. Hence, this study was intended to evaluate the bioactive seaweed sulfated polysaccharides (SSP) against the ompF (outer membrane porin F) protein target of Salmonella typhi. SSP are sulfated compounds with a wide range of biological activities, such as anti-microbial, anti-allergy, anti-cancer, anti-coagulant, anti-inflammation, anti-oxidant, and anti-viral. Results: In this study, eleven compounds were targeted against S. typhi OmpF by molecular docking approach and were compared with two commercially available typhoid medications. The SSP showed good binding affinity compared to commercial drugs, particularly carrageenan/MIV-150, carrageenan lambda, fucoidan, and 3-Phenyllactate, ranked as top antagonists against OmpF. Further, pharmacokinetics and toxicology (ADMET) studies corroborated that SSP possessed drug-likeness and highly progressed in all parameters.Conclusion: AutoDockTools and Schrodinger's QikProp module results suggest that SSP could be a promising drug for extensively drug-resistant (XDR) S. typhi. To our best of knowledge, this is the first report on in-silico analysis of SSP against S. typhi OmpF. Thus, implying the capabilities of SSP's especially compounds like carrageenans, as a potential anti-microbial agent against Salmonella typhi infections. Eventually, advanced studies could corroborate SSPs to the next level of application in the crisis of XDR microbial diseases.

scholarly journals Evaluation of seaweed sulfated polysaccharides as natural antagonists targeting Salmonella typhi OmpF: molecular docking and pharmacokinetic profiling

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Malaisamy Arunkumar ◽  
Murugan Mahalakshmi ◽  
Vairamuthu Ashokkumar ◽  
Manikka Kubendran Aravind ◽  
Sathaiah Gunaseelan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Pathogenic Bacteria ◽  
Biological Activities ◽  
Salmonella Typhi ◽  
Sulfated Polysaccharides ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Microbial Diseases ◽  
Wide Range ◽  
Docking Approach

Abstract Background Salmonella belongs to the Enterobacteriaceae family, a gram-negative, non-spore-forming, rod-shaped, motile, and pathogenic bacteria that transmit through unhygienic conditions. It is estimated that 21 million new infections arise every year, resulting in approximately 200,000 deaths. It is more prevalent among children, the old aged, and immunocompromised individuals. The frequent usage of classical antimicrobials has begun the increasing emergence of various drug-resistant pathogenic bacterial strains. Hence, this study was intended to evaluate the bioactive seaweed sulfated polysaccharides (SSPs) against the ompF (outer membrane porin F) protein target of Salmonella typhi. SSP is the sulfated compound with a wide range of biological activities, such as anti-microbial, anti-allergy, anti-cancer, anti-coagulant, anti-inflammation, anti-oxidant, and anti-viral. Results In this study, eleven compounds were targeted against S. typhi OmpF by the molecular docking approach and were compared with two commercially available typhoid medications. The SSP showed good binding affinity compared to commercial drugs, particularly carrageenan/MIV-150, carrageenan lambda, fucoidan, and 3-phenyllactate, ranked as top antagonists against OmpF. Further, pharmacokinetics and toxicology (ADMET) studies corroborated that SSP possessed drug-likeness and highly progressed in all parameters. Conclusions AutoDockTools and Schrodinger's QikProp module results suggest that SSP could be a promising drug for extensively drug-resistant (XDR) S. typhi. To the best of our knowledge, this is the first report on in silico analysis of SSP against S. typhi OmpF, thus implying the capabilities of SSPs especially compounds like carrageenans, as a potential anti-microbial agent against Salmonella typhi infections. Eventually, advanced studies could corroborate SSPs to the next level of application in the crisis of XDR microbial diseases. Graphical Abstract

scholarly journals Isoniazid-Isatin Hydrazone Derivatives: Synthesis, Antitubercular Activity and Molecular Docking Studies

2021 ◽  
Vol 18 (21) ◽  
pp. 39
Author(s):  
Mardi Santoso ◽  
Muhammad Riza Ghulam Fahmi ◽  
Yehezkiel Steven Kurniawan ◽  
Taslim Ersam ◽  
Sri Fatmawati ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Active Site ◽  
Antitubercular Activity ◽  
Docking Study ◽  
Positive Control ◽  
Tuberculosis H37rv ◽  
Molecular Docking Study

This study examined the synthesis of isoniazid-isatin hydrazone derivatives 5-7, followed by an investigation on the in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, and molecular docking. A yield of 81 - 92 % of these compounds was achieved, with structural characterization by spectroscopic methods (FTIR, NMR, HRMS). The in vitro antitubercular activity was evaluated against M. tuberculosis H37Rv, and the highest effect was observed in compound 7, with a minimum inhibitory concentration (MIC) of 0.017 mM, lower than rifampicin (MIC 0.048 mM), which served as the positive control. In addition, the molecular docking of 5-7 was performed to visualize the interaction of isoniazid-isatin hydrazone derivatives with the active site of InhA receptor, which was in agreement with the experimental data. The hydrogen bonding with Ser94 and pi-pi interaction with Phe41 and/or Phe97 on the InhA active site was pivotal for the antitubercular activity. HIGHLIGHTS Tuberculosis caused by Mycobacterium tuberculosis is one of the top ten leading causes of death globally The first and second lines of antituberculosis drugs are the prevalent treatment for this disease, but they show several drawbacks and are exacerbated by the occurrence of drug resistance The isoniazid-isatin hydrazone derivatives were designed through molecular hybridization and synthesized effectively and exhibited moderate to high activity against tuberculosis H37Rv Molecular docking study demonstrated that the hydrogen bonding with Ser94 and the pi-pi interaction with Phe41 and/or Phe97 are important for antitubercular activity GRAPHICAL ABSTRACT

Identification and Characterisation of Two 1-Aminocyclopropane- 1-Carboxylate (ACC) Synthase cDNAs Expressed during Papaya (Carica papaya) Fruit Ripening

1997 ◽  
Vol 24 (2) ◽  
pp. 239 ◽  
Author(s):  
Michael Glenn Mason ◽  
José Ramón Botella
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Fruit Ripening ◽  
Active Site ◽  
Carica Papaya ◽  
Expression Patterns ◽  
Acc Synthase ◽  
Single Copy ◽  
Mrna Levels ◽  
Amino Acid Residues

The cloning and characterisation of two cDNAs (capacs1 and capacs2) encoding ACC synthase in papaya (Carica papaya L.) is described. capacs1 is 1104 bp long encoding 368 amino acids. capacs2 is 1098 bp long encoding 366 amino acids. The proteins encoded by both cDNAs contain the highly conserved active site of ACC synthases as well as 10 (capacs1) or 11 (capacs2) of the 12 amino acid residues conserved in most aminotransferases. Southern analyses indicate that capacs1 and capacs2 are present in the papaya genome as single copy genes. Both genes show very different expression patterns during fruit ripening. capacs1 mRNA levels are high in mature green fruits, decreasing steadily during ripening, whereas capacs2 mRNA levels are undetectable in mature green fruits but experience a dramatic increase with the onset of ripening and remain high throughout the various stages of ripening.

scholarly journals MOLECULAR DYNAMICS SIMULATIONS OF SEVERAL SELECTED COMPOUNDS FROM THE HERBAL DATABASE OF INDONESIA RESULTS OF MOLECULAR DOCKING AGAINST DNA METHYLTRANSFERASE ENZYME

2018 ◽  
Vol 10 (1) ◽  
pp. 285
Author(s):  
Muhamad Fikri Ihsan ◽  
Arry Yanuar
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamic Simulation ◽  
Molecular Dynamic ◽  
Dynamic Simulation ◽  
Dna Methyltransferase ◽  
Positive Control ◽  
Amino Acid Residues ◽  
Dynamics Simulations ◽  
Ucsf Chimera

Objective: This study aimed to investigate the interactions of DNA methyltransferase (DNMT) enzymes and potential ligands as DNMT inhibitorsthrough molecular dynamics simulations.Methods: This study was conducted using tools in the form of hardware (primary and secondary computers) and software (OpenBabel, AutoDockTools, Amber MD, Amber Tools, VMD, PuTTY, LigandScout, and UCSF Chimera).Results: Results of molecular docking of cassiamin C, procyanidin B2, epicatechin-4alphaent-8-ent-epicatechin, epicatechin-4beta-8-epicatechin-3-O-gallate, neorhusflavanone, 3-O-galloylepigallocatechin -4beta-6-epicatechin-3-O-gallate, withanolide, 3-O-galloylepigallocatechin-4beta-6-epigallocatechin-3-O-gallate, cyanidin-3-6″-caffeylsophoroside-5-glucoside, epifriedelinol, gallocatechin-4alpha-8-epicatechin, scutellarein-7-glucosyl-1-4-rhamnoside, epigallocatechin-3-gallate (EGCG) (positive control), and sinefungin (co-crystal) compounds showed ΔG values −9.34,−10.95, −7.95, −11.01, −8.78, −8.87, −11.49, −7.98, −5.92, −8.92, −9.17, −8.76, −9.70, and −9.11 kcal/mol, respectively. Cassiamin C, procyanidin B2,epicatechin-4-beta-8-epicatechin-3-O-gallate, withanolide, and gallocatechin-4alpha-8-epicatechin compounds had lower ΔG than sinefungin (cocrystal)and EGCG (positive control) compounds. The results of molecular dynamic simulation of seven selected compounds showed the best overallactivities were procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, and gallocatechin-4alpha-8-epi-catechin compounds.Conclusions: The best overall activities based on molecular docking and molecular dynamic simulation were procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, and gallocatechin-4alpha-8-epi-catechin compounds. Amino acid residues that are important for the activity of DNMT1inhibitor are Phe1145, Glu1168, Met1169, Cys1191, Glu1266, Ala1579, and Val1580.

scholarly journals Crystal Structure of d-Hydantoinase from Burkholderia pickettii at a Resolution of 2.7 Angstroms: Insights into the Molecular Basis of Enzyme Thermostability

2003 ◽  
Vol 185 (14) ◽  
pp. 4038-4049 ◽  
Author(s):  
Zhen Xu ◽  
Yunqing Liu ◽  
Yunliu Yang ◽  
Weihong Jiang ◽  
Eddy Arnold ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Amino Acids ◽  
Active Site ◽  
Molecular Basis ◽  
Bacillus Stearothermophilus ◽  
Sequence Similarity ◽  
Amino Acid Residues ◽  
Salt Bridges ◽  
Aromatic Residues ◽  
Catalytic Active Site

ABSTRACT d-Hydantoinase (d-HYD) is an industrial enzyme that is widely used in the production of d-amino acids which are precursors for semisynthesis of antibiotics, peptides, and pesticides. This report describes the crystal structure of d-hydantoinase from Burkholderia pickettii (HYDBp) at a 2.7-Å resolution. The structure of HYDBp consists of a core (α/β)8 triose phosphate isomerase barrel fold and a β-sheet domain, and the catalytic active site consists of two metal ions and six highly conserved amino acid residues. Although HYDBp shares only moderate sequence similarity with d-HYDs from Thermus sp. (HYDTsp) and Bacillus stearothermophilus (HYDBst), whose structures have recently been solved, the overall structure and the structure of the catalytic active site are strikingly similar. Nevertheless, the amino acids that compose the substrate-binding site are less conserved and have different properties, which might dictate the substrate specificity. Structural comparison has revealed insights into the molecular basis of the differential thermostability of d-HYDs. The more thermostable HYDTsp contains more aromatic residues in the interior of the structure than HYDBp and HYDBst. Changes of large aromatic residues in HYDTsp to smaller residues in HYDBp or HYDBst decrease the hydrophobicity and create cavities inside the structure. HYDTsp has more salt bridges and hydrogen-bonding interactions and less oxidation susceptible Met and Cys residues on the protein surface than HYDBp and HYDBst. Besides, HYDTsp also contains more rigid Pro residues. These factors are likely to make major contributions to the varying thermostability of these enzymes. This information could be exploited in helping to engineer more thermostable mesophilic enzymes.

Allosteric inhibition of VIM metallo-β-lactamases by a camelid nanobody

2013 ◽  
Vol 450 (3) ◽  
pp. 477-486 ◽  
Author(s):  
Jean S. Sohier ◽  
Clémentine Laurent ◽  
Andy Chevigné ◽  
Els Pardon ◽  
Vasundara Srinivasan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Binding Site ◽  
Active Site ◽  
Substrate Inhibition ◽  
Inhibition Mechanism ◽  
Bacterial Strains ◽  
Single Domain Antibody ◽  
Alanine Scan ◽  
Hydrophobic Amino Acids ◽  
Micromolar Range

MβL (metallo-β-lactamase) enzymes are usually produced by multi-resistant Gram-negative bacterial strains and have spread worldwide. An approach on the basis of phage display was used to select single-domain antibody fragments (VHHs, also called nanobodies) that would inhibit the clinically relevant VIM (Verona integron-encoded MβL)-4 MβL. Out of more than 50 selected nanobodies, only the NbVIM_38 nanobody inhibited VIM-4. The paratope, inhibition mechanism and epitope of the NbVIM_38 nanobody were then characterized. An alanine scan of the NbVIM_38 paratope showed that its binding was driven by hydrophobic amino acids. The inhibitory concentration was in the micromolar range for all β-lactams tested. In addition, the inhibition was found to follow a mixed hyperbolic profile with a predominantly uncompetitive component. Moreover, substrate inhibition was recorded only after nanobody binding. These kinetic data are indicative of a binding site that is distant from the active site. This finding was confirmed by epitope mapping analysis that was performed using peptides, and which identified two stretches of amino acids in the L6 loop and at the end of the α2 helix. Because this binding site is distant from the active site and alters both the substrate binding and catalytic properties of VIM-4, this nanobody can be considered as an allosteric inhibitor.

scholarly journals Interactions of Alkyl Gallates with SARS-CoV-2 Main Protease: A Molecular Docking Approach

2020 ◽  
Vol 3 (1) ◽  
pp. 9
Author(s):  
Amalia Stefaniu ◽  
Lucia Pintilie ◽  
Bujor Albu ◽  
Lucia Pirvu
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Synthetic Compounds ◽  
X Ray ◽  
Lipinski’S Rule ◽  
Alkyl Gallates ◽  
Main Protease ◽  
Docking Approach ◽  
Lipinski’S Rule Of Five ◽  
In Silico Methods

Ten natural and semi-synthetic compounds (gallic acid and alkyl gallates) were investigated by in silico methods in order to evaluate their potential inhibitory activity against SAR-CoV-2 using the X-ray structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 Å (PDB ID: 6WNP). The evaluation of drug-likeness in terms of Lipinski’s Rule of Five and docking results in terms of docking score and interactions with the amino acids residues from the active binding site of the target protein were reported.

scholarly journals Herbal Compounds from Syzygium aromaticum and Cassia acutifolia as a Shield against SARS-CoV-2 Mpro: a Molecular Docking Approach

2021 ◽  
Vol 11 (6) ◽  
pp. 14853-14865
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
New Drugs ◽  
In Vivo Studies ◽  
Syzygium Aromaticum ◽  
Amino Acid Residues ◽  
Ligand Interaction ◽  
Docking Approach ◽  
Novel Coronavirus

Novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was first identified in China in December 2019. Currently, the novel coronavirus disease 2019 (COVID-19) is the most infectious disease worldwide. In the absence of a vaccine or drug, herbal compounds may be used to treat or control this disease. To explore novel potent inhibitors that suppress this virus's growth, we performed molecular docking studies on SARS-CoV-2 Mpro using 17 effective herbal compounds, along with three reference drugs. Docking results showed that crategolic acid from Syzygium aromaticum (clove) had the highest binding affinity with SARS-CoV-2 Mpro protease, followed by sennoside (A, B, C, and D) compounds from Cassia acutifolia (Sana Makki). Crategolic acid and sennoside (A, B, C, and D) contain amino acid residues and hydrogen bonds involved in the protein-ligand interaction. The present study confirms that crategolic acid and sennoside represent the strongest potential inhibitors of SARS-CoV-2 Mpro. This study's results may help in vivo studies validate the usefulness of compounds from clove and Sana Makki in preparing herbal medicine for the treatment of COVID-19. This analysis supports the production of new drugs for the treatment and control of COVID-19.

scholarly journals The potency of blumeatin and luteolin as caspase-1 inhibitor by molecular docking

2022 ◽  
Vol 2 (1) ◽  
pp. 22
Author(s):  
I Putu Ari Anggara Catur Pratama ◽  
I Made Harimbawa Putra ◽  
Luh Wayan Sita Pujasari ◽  
Komang Dian Merta Sari Dewi ◽  
Ni Putu Linda Laksmiani
Keyword(s):  
Molecular Docking ◽  
Amino Acid Residues ◽  
Caspase 1 ◽  
Protocol Validation ◽  
Docking Protocol ◽  
Tnf Α ◽  
Docking Approach ◽  
Ifn Γ ◽  
Anti Inflammation ◽  
Native Ligand

COVID-19 infection induces inflammation by increasing cytokines such as IL-1b, IL-6, IL-18, IFN-γ, and TNF-α. IL-1b is generated by the involvement of caspase-1. Therefore, caspase-1 inhibitor can be potential for inflammation therapy caused by COVID-19 infection. This study aims to determine the potential of blumeatin and luteolin as anti-inflammatory agents by inhibiting caspase-1 using a molecular docking approach. This study was carried out by caspase-1 (PDB ID: 1RWK) preparation, blumeatin and luteolin structure optimization, docking protocol validation, and docking of blumeatin and luteolin on caspase-1. Bluematin and luteolin had a binding affinity of -5,63 kcal/mol and -5,93 kcal/mol, lower than Q158 native ligand (-3.92 kcal/mol). Similar amino acid residues in hydrogen bonds interaction were observed between Q158 native ligand, blumeatin, and luteolin with caspase-1 (GLN 283 and ARG 179). Blumeatin and luteolin are potentially anti-inflammation agents through the inhibition of the caspase-1 in silico.

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