In silico bioprospecting of receptors for Doderlin: an antimicrobial peptide isolated from Lactobacillus acidophilus

In Silico Pharmacology - Tập 11 - Trang 1-11 - 2023
Elias Jorge Muniz Seif1,2, Marcelo Yudi Icimoto3, Pedro Ismael da Silva Junior1,2
1Postgraduate Program in Molecular Biology, Federal University of São Paulo, São Paulo, Brazil
2Laboratory for Applied Toxinology (LETA), Center of Toxins, Immune-Response and Cell Signaling (CETICS/CEPID), Butantan Institute, São Paulo, Brazil
3Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil

Tóm tắt

The emergence of resistant bacteria strains against traditional antibiotics and treatments increases each year. Doderlin is a cationic and amphiphilic peptide active against gram-positive, negative and yeast stains. The aim of the present work was prospect potentials receptors associated of antimicrobial activity of Doderlin using in silico bioinformatics tools. To search for potential targets of Doderlin, PharmMapper software was used. Molecular docking between Doderlin and the receptor was performed by PatchDock. Additional interaction and ligand site prediction for each receptor was performed by I-TASSER software. Those PDB Id, 1XDJ (score: 11,746), 1JMH (score: 11,046), 1YR3 (score: 10,578), 1NG3 (score: 10,082) showed highest dock score. Doderlin was found to predicted/real sites co-localize with 1XDJ and 1JMH, enzymes accountable for nitrogenic bases synthesis. The resulting receptor bioprospecting is highly correlated and suggests that Doderlin might act by interfering with DNA metabolism/production of bacteria, altering microorganism homeostasis and growth impairment.

Tài liệu tham khảo

Bhattacharya A et al (2021) Combined gene deletion of dihydrofolate reductase-thymidylate synthase and pteridine reductase in leishmania infantum. PLoS Negl Trop Dis 15:e0009377 Cani PD et al (2019) Microbial regulation of organismal energy homeostasis. Nat Metab 1:34–46 Coburn B et al (2007) Salmonella, the host and disease: a brief review. Immunol Cell Biol 85:112–118 Craik DJ et al (2013) The future of peptide-based drugs. Chem Biol Drug Des 81:136–147 Dandanell G et al (2005) Escherichia coli purine nucleoside phosphorylase II, the product of the xapA gene. J Mol Biol 348:113–125 Deobald D et al (2020) Identification and characterization of a bacterial core methionine synthase. Sci Rep 10:1–13 Diniz LCL et al (2018) Human antimicrobial peptide isolated from Triatoma infestans Haemolymph, Trypanosoma cruzi-transmitting vector. Front Cell Infect Microbiol 8:354 Ehrenstein G, Lecar H (1977) Electrically gated ionic channels in lipid bilayers. Q Rev Biophys 10:1–34 Epand RM et al (2016) Molecular mechanisms of membrane targeting antibiotics. Biochim Biophys Acta Biomembr 1858:980–987 FADAHUNSI OS et al (2022) Angiotensin converting enzyme inhibitors from medicinal plants: a molecular docking and dynamic simulation approach. In Silico Pharmacology, vol. 10, no. 1 Fox KM et al (2008) Crystal structure of thymidylate synthase A from Bacillus subtilis. Protein Sci 8:538–544 Gautier R et al (2008) HELIQUEST: a web server to screen sequences with specific α-helical properties. Bioinformatics 24:2101–2102 Gould IM, Bal AM (2013) New antibiotic agents in the pipeline and how they can help overcome microbial resistance. Virulence 4:185–191 Hopkins AL et al (2014) The role of ligand efficiency metrics in drug discovery. Nat Rev Drug Discov 13:105–121 Iyer P et al (2015) In silico identification of targets for a novel scaffold, 2-thiazolylimino-5-benzylidin-thiazolidin-4-one. Mol Divers 19:855–870 Larru B, Gerber JS (2014) Cutaneous bacterial infections caused by Staphylococcus aureus and Streptococcus pyogenes in infants and children. Pediatr Clin North Am 61:457–478 Le CF et al (2017) Intracellular targeting mechanisms by antimicrobial peptides. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.02340-16 Lin S et al (2022) Vitamin B12-auxotrophy in dinoflagellates caused by incomplete or absent cobalamin-independent methionine synthase genes (metE). Fundam Res 2:727–737 Ludtke SJ et al (1996) Membrane pores induced by magainin. Biochemistry 35:13723–13728 Marie E et al (2014) Amphiphilic macromolecules on cell membranes: from protective layers to controlled permeabilization. J Membr Biol 247:861–881 Marx W et al (2021) Diet and depression: exploring the biological mechanisms of action. Mol Psychiatry 26:134–150 Mettai M et al (2023) Molecular docking/dynamics simulations, MEP analysis, bioisosteric replacement and ADME/T prediction for identification of dual targets inhibitors of Parkinson’s disease with novel scaffold. Silico Pharmacol 11(1):3. https://doi.org/10.1007/s40203-023-00139-3 Murray CJ et al (2022) Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399:629–655 Nevola L, Giralt E (2015) Modulating protein–protein interactions: the potential of peptides. Chem Commun 51:3302–3315 Nicolas P (2009) Multifunctional host defense peptides: intracellular-targeting antimicrobial peptides. FEBS J 276:6483–6496 Nicolas P, El Amri C (2009) The dermaseptin superfamily: a gene-based combinatorial library of antimicrobial peptides. Biochim Biophys Acta Biomembr 1788:1537–1550 Ntwasa M (2012) Cationic peptide interactions with biological macromolecules. In: Binding protein, pp 139-164 O’Neill J (2016) Review on antimicrobial resistance: tackling drug-resistant infections globally: final report and recommendations. In: Rev. Antimicrob. Resist. tackling drug-resistant Infect. Glob. Final Rep. Recomm Pejchal R, Ludwig ML (2005) Cobalamin-independent methionine synthase (MetE): a face-to-face double barrel that evolved by gene duplication. PLoS Biol 3:0254–0265 Pelay-Gimeno M et al (2015) Structure-based design of inhibitors of protein–protein interactions: mimicking peptide binding epitopes. Angew Chemie - Int Ed 54:8896–8927 Pettersen EF et al (2004) UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612 Pouny Y et al (1992) Interaction of antimicrobial Dermaseptin and its fluorescently labeled analogs with phospholipid membranes. Biochemistry 31:12416–12423 Pozzi C et al (2019) Targeting methyltransferases in human pathogenic bacteria: insights into thymidylate synthase (TS) and flavin-dependent TS (FDTs). Molecules 24:1638 Sakamoto K (2012) The pathology of Mycobacterium tuberculosis infection. Vet Pathol 49:423–439 Schneidman-Duhovny D et al (2005) PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Research 33:W363–W367 Settembre EC et al (2003) Structural and mechanistic studies on thiO, a glycine oxidase essential for thiamin biosynthesis in Bacillus subtilis. Biochemistry 42:2971–2981 Shahid M et al (2021) Comprehensive computational target fishing approach to identify Xanthorrhizol putative targets. Sci Rep 11:1594 Silva BS et al (2023) Doderlin: isolation and characterization of a broad-spectrum antimicrobial peptide from Lactobacillus acidophilus. Res Microbiol 174:103995 Timofeev VI et al (2022) The comparative analysis of the properties and structures of purine nucleoside phosphorylases from thermophilic bacterium Thermus thermophilus HB27. J Biomol Struct Dyn 40:3626–3641 Utama GL et al (2019) Probiotic candidates yeast isolated from Dangke—Indonesian traditional fermented buffalo milk. Acta Univ Agric Silvic Mendelianae Brun 67:179–187 Wakchaure PD, Ganguly B (2023) Exploring the structure, function of thiamine pyrophosphate riboswitch, and designing small molecules for antibacterial activity. WIREs RNA, e1774. Wang X et al (2017) PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res 45:W356–W360 Wenzel M et al (2014) Small cationic antimicrobial peptides delocalize peripheral membrane proteins. In: Proceedings of the National Academy of Sciences, vol. 111, no. 14, p. E1409–E1418 Zheng W et al (2021) Folding non-homologous proteins by coupling deep-learning contact maps with I-TASSER assembly simulations. Cell Rep Methods 1