Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
The Outward Shift of Clarithromycin Binding to the Ribosome in Mutant Helicobacter Pylori Strains Publisher Pubmed



Salehi N1 ; Attaran B2, 3 ; Zaremirakabad F4 ; Ghadiri B2 ; Esmaeili M2 ; Shakaram M2 ; Tashakoripour M5 ; Eshagh Hosseini M5 ; Mohammadi M2
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
  2. 2. HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  3. 3. Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
  4. 4. Department of Mathematics and Computer Science, Amirkabir University of Technology, Tehran, Iran
  5. 5. Gastroenterology Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: Helicobacter Published:2020


Abstract

Objectives: Disruption of protein synthesis, by drug-mediated restriction of the ribosomal nascent peptide exit tunnel (NPET), may inhibit bacterial growth. Here, we have studied the secondary and tertiary structures of domain V of the 23S rRNA in the wild-type and mutant (resistant) H. pylori strains and their mechanisms of interaction with clarithromycin (CLA). Methods: H pylori strains, isolated from cultured gastric biopsies, underwent CLA susceptibility testing by E test, followed by PCR amplification and sequencing of domain V of 23S rRNA. The homology model of this domain in H pylori, in complex with L4 and L22 accessory proteins, was determined based on the E. coli ribosome 3D structure. The interactions between CLA and 23S rRNA complex were determined by molecular docking studies. Results: Of the 70 H pylori strains, isolated from 200 dyspeptic patients, 11 (16%) were CLA-resistant. DNA sequencing identified categories with no (A), A2142G (B), and A2143G (C) mutations. Docking studies of our homology model of 23S rRNA complex with CLA showed deviated positions for categories B and C, in reference to category A, with 12.19 A and 7.92 A RMSD values, respectively. In both mutant categories, CLA lost its interactions at positions 2142 and 2587 and gained two new bonds with the L4 accessory protein. Conclusion: Our data suggest that, in mutant H pylori strains, once the nucleotides at positions 2142 and 2587 are detached from the drug, CLA interacts with and is peeled back by the L4 accessory protein, removing the drug-imposed spatial restriction of the NPET. © 2020 John Wiley & Sons Ltd
Related Docs
View other Related Docs
1. The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes, Gut Pathogens (2021)
2. Identification of Uba1 As the Causative Gene of an X-Linked Non-Kennedy Spinal–Bulbar Muscular Atrophy, European Journal of Neurology (2022)
3. Mechanism of Action, Resistance, Synergism, and Clinical Implications of Azithromycin, Journal of Clinical Laboratory Analysis (2022)
4. Novel Stag3 Variant Associated With Primary Ovarian Insufficiency and Non-Obstructive Azoospermia in an Iranian Consanguineous Family, Gene (2022)
5. Fluorescence Labeling of Anchor-Modified Mart-1 Peptide for Increasing Its Affinity for Hla-A*0201: Hit Two Targets With One Arrow, Journal of Peptide Science (2023)
6. Targeting Caspases 3/6 and Cathepsins L/B May Decrease Laminopathy-Induced Apoptosis in Alzheimer’S Disease, Journal of Alzheimer's Disease (2024)
7. Design and Synthesis of Heterocyclic Azole Based Bioactive Compounds: Molecular Structures, Quantum Simulation, and Mechanistic Studies Through Docking As Multi-Target Inhibitors of Sars-Cov-2 and Cytotoxicity, Journal of Molecular Structure (2022)
8. 3D-Qsar, Molecular Docking, and Molecular Dynamic Simulations for Prediction of New Hsp90 Inhibitors Based on Isoxazole Scaffold, Journal of Biomolecular Structure and Dynamics (2018)
Experts (# of related papers)
View all Related Experts
Massoud Amanlou (8)
Somayeh Mojtabavi (2)
Other Related Docs
9. Characterization of the Dna Mismatch Repair Proteins Muts and Mutl in a Hypermutator Acinetobacter Baumannii, Microbial Pathogenesis (2017)
10. 3,4-Dihydropyrimidin-2(1H)-One C5 Amides As Inhibitors of T Nfα Production: Synthesis, Biological Evaluation and Molecular Modeling, Letters in Drug Design and Discovery (2017)
11. Rational Design of Anti-Angiogenic Peptides to Inhibit Vegf/Vegfr2 Interactions for Cancer Therapeutics, Anti-Cancer Agents in Medicinal Chemistry (2022)
12. A Novel Autosomal Recessive Gjb2-Associated Disorder: Ichthyosis Follicularis, Bilateral Severe Sensorineural Hearing Loss, and Punctate Palmoplantar Keratoderma, Human Mutation (2019)
13. Zeolite Nanoparticles Inhibit Aβ-Fibrinogen Interaction and Formation of a Consequent Abnormal Structural Clot, ACS Applied Materials and Interfaces (2016)
14. Inhibition of Liver Alanine Aminotransferase and Aspartate Aminotransferase by Hesperidin and Its Aglycone Hesperetin: An in Vitro and in Silico Study, Life Sciences (2017)
15. Identification of New Hsp90 Inhibitors: Structure Based Virtual Screening, Molecular Dynamic Simulation, Synthesis and Biological Evaluation, Anti-Cancer Agents in Medicinal Chemistry (2021)
16. Repurposing of the Approved Small Molecule Drugs in Order to Inhibit Sars-Cov-2 S Protein and Human Ace2 Interaction Through Virtual Screening Approaches, Journal of Biomolecular Structure and Dynamics (2022)
17. Atypical Presentations in an Rtd Patient and Report of Novel Slc52a3 and Slc52a2 Mutations, Acta Neurologica Belgica (2024)
18. Extraction and Identification of Two Flavonoids in Phlomoides Hyoscyamoides As an Endemic Plant of Iran: The Role of Quercetin in the Activation of the Glutathione Peroxidase, the Improvement of the Hydroxyproline and Protein Oxidation in Bile Duct-Ligated Rats, Current Computer-Aided Drug Design (2020)
19. Design, Synthesis, Docking Study and Urease Inhibitory Activity Evaluation of Novel 2-((5-Amino-1,3,4-Thiadiazol-2-Yl)Thio)-N-Arylacetamide Derivatives, Medicinal Chemistry Research (2021)
20. Qsar and Docking Studies on the (5-Nitroheteroaryl-1,3,4-Thiadiazole-2-Yl) Piperazinyl Analogs With Antileishmanial Activity, Journal of Chemometrics (2016)
21. Efficacy of Pyloshot in Combination With Standard Four-Drug Antimicrobial Treatment for Helicobacter Pylori Eradication: A Randomized Clinical Trial, JGH Open (2024)
22. Lipase@Zeolitic Imidazolate Framework Zif-90: A Highly Stable and Recyclable Biocatalyst for the Synthesis of Fruity Banana Flavour, International Journal of Biological Macromolecules (2021)
23. In Silico Analysis of Novel Mutations in Maple Syrup Urine Disease Patients From Iran, Metabolic Brain Disease (2017)
24. Spherical Peg/Sio2 Promising Agents for Lamivudine Antiviral Drug Delivery, a Molecular Dynamics Simulation Study, Scientific Reports (2023)
25. Elucidation of Molecular Mechanisms Behind the Self-Assembly Behavior of Chitosan Amphiphilic Derivatives Through Experiment and Molecular Modeling, Pharmaceutical Research (2015)
26. Identification of Phytochemicals Targeting C-Met Kinase Domain Using Consensus Docking and Molecular Dynamics Simulation Studies, Cell Biochemistry and Biophysics (2018)
27. Novel Pyrano[3,2-C]Quinoline-1,2,3-Triazole Hybrids As Potential Anti-Diabetic Agents: In Vitro Α-Glucosidase Inhibition, Kinetic, and Molecular Dynamics Simulation, ACS Omega (2023)
28. Maple Syrup Urine Disease Mutation Spectrum in a Cohort of 40 Consanguineous Patients and Insilico Analysis of Novel Mutations, Metabolic Brain Disease (2019)
29. In Silico Designing of a New Cysteine Analogue of Hirudin Variant 3 for Site Specific Pegylation, Research in Pharmaceutical Sciences (2017)
30. Biological Evaluation of 9-(1H-Indol-3-Yl) Xanthen-4-(9H)-Ones Derivatives As Noncompetitive Α-Glucosidase Inhibitors: Kinetics and Molecular Mechanisms, Structural Chemistry (2019)
31. Consensus Virtual Screening to Propose Antivirals From Myrtus Communis L. Against Human Papillomavirus: Machine Learning and Docking, Journal of Molecular Liquids (2025)
32. Structural and Dynamic Insight Into Hirudin Epitopes-Hla-Drb1 0101 Complexes and Their Modified Peptide Ligands: A Molecular Dynamic Simulation Study, Tropical Journal of Pharmaceutical Research (2015)
33. Arylhydrazone Derivatives of Naproxen As New Analgesic and Anti-Inflammatory Agents: Design, Synthesis and Molecular Docking Studies, Journal of Molecular Graphics and Modelling (2016)
34. Efficacy and Tolerability of Two Quadruple Regimens: Bismuth, Omeprazole, Metronidazole With Amoxicillin or Tetracycline As First-Line Treatment for Eradication of Helicobacter Pylori in Patients With Duodenal Ulcer: A Randomized Clinical Trial, PLoS ONE (2018)
35. A Structural Model of the Anaphase Promoting Complex Co-Activator (Cdh1) and in Silico Design of Inhibitory Compounds, Research in Pharmaceutical Sciences (2015)
36. Rational Design of Stable and Functional Hirudin Iii Mutants With Lower Antigenicity, Biologicals (2015)
37. Gene-Targeted Next Generation Sequencing Identifies Pnpla1 Mutations in Patients With a Phenotypic Spectrum of Autosomal Recessive Congenital Ichthyosis: The Impact of Consanguinity, Journal of Investigative Dermatology (2017)
38. Synthesis, Molecular Docking, and Biological Evaluation of Nitroimidazole Derivatives As Potent Urease Inhibitors, Medicinal Chemistry Research (2021)
39. Design, Synthesis, and Evaluation of Novel Racecadotril-Tetrazole-Amino Acid Derivatives As New Potent Analgesic Agents, Research in Pharmaceutical Sciences (2021)
40. Identification of New Dna Gyrase Inhibitors Based on Bioactive Compounds From Streptomyces: Structure-Based Virtual Screening and Molecular Dynamics Simulations Approaches, Journal of Biomolecular Structure and Dynamics (2020)
41. Azoridactase Enzyme Engineering to Induce Structural Changes in the Active Site and Improve Its Affinity for Azo Dyes, Journal of Knowledge and Health in Basic Medical Sciences (2024)