In silico screening of natural products targeting chorismate synthase

Keywords: Amentoflavone, Docking, Homology modeling, Pharmacokinetics

Abstract

Introduction: Chorismate synthase catalyzes the final step in shikimate acid pathway involved in synthesis of aromatic compounds in bacteria. This enzyme can be a possible molecular target for design of antibiotics. Materials and Methods: Homology modeling and molecular docking were performed to screen about one hundred natural compounds in order to find inhibitors of enzymes as a possible new target. A model was built by SWISS-MODEL and its quality was assessed by ERRAT, ProSA, Rampage and MolProbity servers. Docking experiments were performed and pharmacokinetics and toxicities were studied by admetSAR. Results: The predicted model was reliable to be used in docking experiments. Amentoflavone had the highest binding affinity of -10.0 Kcal/mol. Probabilities indicated that rotenone may inhibit P-glycoprotein I, hinokiflavone and silybin may inhibit P-glycoprotein II, while taspine acts on both types of P-glycoproteins. Amentofalavone, hinokiflavone, rotenone and silybin have a probability of inhibiting cytochromes that are involved in oxidation stage of metabolism. Conclusions: These compounds had binding affinities towards FMN binding site of the enzyme model and may be considered in the research for new antibacterial agents but only when their drug interactions are fully investigated.

References

Yarwood JM, Schlievert PM. Quorum sensing in Staphylococcus infections. J Clin Invest. 2003. 112: 1620-25. https://doi.org/10.1172/JCI20442

Tong SY, Davis JS, Eichenberger E, Holland TL, Flower Jr VG. Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015. 28:603-61. https://doi.org/10.1128/CMR.00134-14

Kaneko J, kamio Y. Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures pore-forming mechanism organization of the genes. Biosci Biotechnol Biochem. 2004. 68:981-03. https://doi.org/10.1271/bbb.68.981

Boswihi SS, Udo EE. Methicillin-resistant Staphylococcus aureus: an update on the epidemiology, treatment options and infection control. Curr Med Res Prac. 2018. 8:18-24. https://doi.org/10.1016/j.cmrp.2018.01.001

Al-Dahbi AM, Al-Mathkhury HJ. Distribution of methicillin resistant Staphylococcus aureus in Iraqi patients and healthcare workers. Iraqi J Sci.2013. 54(2):293-300.

Dias MV, Ely F, Palma MS, de Azevedo WF Jr., Basso LA, Santos DS. Chorismate synthase: An attractive target for drug development against orphan diseases. Curr Drug Targets. 2007. 8(3): 437-44. https://doi.org/10.2174/138945007780058924

Macheroux P, Schmid J, Amrhein N, Schaller A. 1999. A unique reaction in a common pathway: mechanism and function of chorismate synthase in the shikimate pathway. Planta. 1999: 207:325-34.

https://doi.org/10.1007/s004250050489

González-Bello C. Inhibition of shikimate kinase and type II dehydroquinase for antibiotic discovery: Structure-based design and simulation studies. Curr Topics Med Chem. 2016. 16:960-77.

https://doi.org/10.2174/1568026615666150825142527

Holden MT, Feil EJ, Lindsay JA, Peacock SJ, Day NP, Enright MC, et al. Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the rapid evolution of virulence and drug resistance. Proc Nat Acad Sci. USA. 2004. 101(26): 9786-91. https://doi.org/10.1073/pnas.0402521101

Källberg M, Wang H, Wang S, Peng J, Wang Z, Lu H, et al. Template-based protein structure modeling using the RaptorX web server. Nat Protocols. 2012. 7:1511-22. https://doi.org/10.1038/nprot.2012.085

Wallace AC, Laskowaski RA, Thornton JM. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 1996. 8:127-34. https://doi.org/10.1093/protein/8.2.127

Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriella G, Gumienny R, et al. SWISS-MODEL: Homology modeling of protein and protein structures and complexes. Nucleic Acid Res. 2018. 46:W296-03. https://doi.org/10.1093/nar/gky427

Colovos C, Yeates TO. Verification of protein structures: Patterns of non-bonded atomic interactions. Protein Sci. 1993. 2:1511-19. https://doi.org/10.1002/pro.5560020916

Wiederstein M, Sippl MJ. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res. 2007. 35: W407-10. https://doi.org/10.1093/nar/gkm290

Lovell SC, Davis IW, Arendall WB 3rd, de Bakker PI, Word JM, Prisant MG, et al. Structure validation by Cα geometry: phi, psi and Cβ deviation. Proteins. 2003. 50(3):437-50. https://doi.org/10.1002/prot.10286

Chen VB, Arendall WB 3rd, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, et al. MolProbity: all atom structure validation for macromolecular crystallography. Acta cryst. 2010. D66:12-21. https://doi.org/10.1107/S0907444909042073

Irwin JJ, Shoichet. ZINC: A free database of commercially available compounds for virtual screening. J Chem Inf Model. 2005. 45:177-82. https://doi.org/10.1021/ci049714

Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem. 2010. 31:455-61. https://doi.org/10.1002/jcc.21334

Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, et al. admetSAR: A comprehensive source and free tool for evaluating chemical ADMET properties. J Chem Inf Model. 2012. 52(11):3099-05. https://doi.org/10.1021/ci300367a

Maclean J, Ali S. The structure of chorismate synthase reveals a novel flavin binding site fundamental to a unique chemical reaction. Structure. 2003. 11:1499-11. https://doi.org/10.1016/j.str.2003.11.005

Sanner MF. Python: A programming language for software integration and development. J Mol Graphics Mod.1999. 17:57-61.

Laskowski RA, MacArthur MW, Moss D and Thornton JM .1993. PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Crystal. 1993. 26:283-91. https://doi.org/10.1107/S0021889892009944

Kelder J, Grootenhuis PDJ, Bayada DM, Delbressine LPC, Ploemen J-P. Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs. Pharm Res. 1999. 16: 1514-19. https://doi.org/10.1023/A:1015040217741

Navia M, Chaturvedi PR. Design principles for orally bioavailable drugs. Drug Discov Today. 1:179-89. https://doi.org/10.1016/1359-6446(96)10020-9

Lipinski CA, Lombardo F, Dominy BW, Feeney P. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001. 46:3-26. https://doi.org/10.1016/S0169-409X(00)00129-0

Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutritional Sci. 2016. 5(e47):1-15. https://doi.org/10.1017/jns.2016.41

Hwang JH, Choi H, Woo E-R, Lee DG. Antibacterial effect of amentoflavone and its synergistic effect with antibiotics. J. Microbiol. Biotechnol. 2013. 23(7): 953-58. https://doi.org/10.4014/jmb.1302.02045

Hossain MM, Roy PK, Jannatul Mosnaz ATM, Shakil SK, Hasan MM, Prodhan SH. Structural analysis and molecular docking of potential ligands with chorismate synthase of Listeria monocytogenes: A novel antibacterial drug target. Indian J Bioch Bioph 2015. 52:45-49.

Kolawole OC. Design and docking studies of inhibitors for the chorismate synthase from Streptococcus pneumoniae using 5-enolpyruvylshikimate-3-phosphate (EPSP) analogues. J Pharma Bioresource. 2015. 12(1):60-76. https://doi.org/10.4314/jpb.v12i1.9

de la Nuez A, Rodríguez R. Current methodology for the assessment of ADME-Tox properties on drug candidate molecules. Biotec Aplic. 2008. 25(2):97-10.

Carpenter TS, Kirshner DA, Lau EY, Wong SE, Nilmeier JP, Lightstone FC. A method to predict blood-brain barrier permeability of drug-like compounds using molecular dynamics simulations. Biophysical J. 2014. 107:630-41. https://doi.org/10.1016/j.bpj.2014.06.024

Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics. Clin Pharmacokint. 2003. 42(1): 59-98. https://doi.org/10.2165/00003088-200342010-00003

Sharom FJ. ABC multidrug transporters: Structure, function and role in chemoresistance. Cancer Biol Ther. 2008. 3:382-84.

Colabufo NA, Berardi F, Cantore M, Contino M, Inglese C, Niso M, et al. Perspectives of P-glycoprotein modulating agents in oncology and neurodegenerative diseases: pharmaceutical, biological, and diagnostic potentials. J Med Chem. 2010. 53(5): 1883-97. https://doi.org/10.1021/jm900743c

Hagos Y, Wolff NA. Assessment of the role of renal organic anion transporters in drug-induced nephrotoxicity. Toxins. 2010. 2: 2055-82. https://doi.org/10.3390/toxins2082055

Published
2019-10-25
How to Cite
Al-Khayyat, M. Z. (2019). In silico screening of natural products targeting chorismate synthase, 7(1), 1-9. https://doi.org/10.15649/2346075X.505
Section
Artículo de investigación científica y tecnológica