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image of Deciphering Plasmodium Condensin Core Subunits of Structural Maintenance of Chromosomes 2 (SMC2) as a Putative Drug Target for Antimalarial Drug

Abstract

Background

The structural maintenance of chromosomes (SMC) proteins plays a noteworthy role in chromosome dynamics. Several recent studies reported that the condensin core subunits of structural maintenance of chromosomes 2 (SMC2) play important roles in the atypical mitosis of the Plasmodium life cycle and may perform different functions during different proliferative stages. For eukaryotes, the structural maintenance of chromosomes (SMC) proteins are divided into six subunits and form three heterodimers of structural maintenance of chromosomes (SMC1/3) cohesion complex, structural maintenance of chromosomes (SMC2/4) condensin complex, and structural maintenance of chromosomes (SMC5/6) complex for chromosome cohesion, condensation, and DNA damage repair, respectively.

Objective

The objective of this study was to investigate the structural maintenance of chromosomes 2 (SMC2) protein of P. falciparum as a putative drug target of malaria-causing Plasmodium falciparum.

Methods: In this study, we investigated the structural maintenance of chromosomes 2 (SMC2) protein of P. falciparum as a putative drug target of malaria-causing P. falciparum by using approaches like Homology modeling, evaluation of the modeled structure, molecular docking study to investigate the interaction of receptor-ligand, and molecular dynamic simulation study with MM calculation.

Results

We reported the structural maintenance of chromosomes 2 (SMC2) protein of P. falciparum as a potent drug target that can pave the way for novel drug discovery to mitigate malaria.

Conclusion

-based studies play a significant role in understanding any protein for potential drug development.

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2024-10-31
2025-04-04

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References

  1. Losada A. Hirano M. Hirano T. Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes Dev. 1998 12 13 1986 1997 10.1101/gad.12.13.1986 9649503
    [Google Scholar]
  2. Thadani R. Kamenz J. Heeger S. Muñoz S. Uhlmann F. Cell-cycle regulation of dynamic chromosome association of the condensin complex. Cell Rep. 2018 23 8 2308 2317 10.1016/j.celrep.2018.04.082 29791843
    [Google Scholar]
  3. Dávalos V. Súarez-López L. Castaño J. Messent A. Abasolo I. Fernandez Y. Guerra-Moreno A. Espín E. Armengol M. Musulen E. Ariza A. Sayós J. Arango D. Schwartz S. Jr Human SMC2 protein, a core subunit of human condensin complex, is a novel transcriptional target of the WNT signaling pathway and a new therapeutic target. J. Biol. Chem. 2012 287 52 43472 43481 10.1074/jbc.M112.428466 23095742
    [Google Scholar]
  4. Ball A.R. Jr Yokomori K. The structural maintenance of chromosomes (SMC) family of proteins in mammals. Chromosome Res. 2001 9 2 85 96 10.1023/A:1009287518015 11321372
    [Google Scholar]
  5. Peters J.M. Tedeschi A. Schmitz J. The cohesin complex and its roles in chromosome biology. Genes Dev. 2008 22 22 3089 3114 10.1101/gad.1724308 19056890
    [Google Scholar]
  6. Pandey R. Abel S. Boucher M. Wall RJ. Zeeshan M. Rea E. Freville A. Lu XM. Brady D. Daniel E. Stanway RR. Wheatley S. Batugedara G. Hollin T. Bottrill AR. Gupta D. Holder AA. Le Roch KG. Tewari R. Plasmodium condensin core subunits SMC2/SMC4 mediate atypical mitosis and are essential for parasite proliferation and transmission. Cell Rep 2020 30 6 1883 1897.e6 10.1016/j.celrep.2020.01.033
    [Google Scholar]
  7. Skibbens R.V. Condensins and cohesins – One of these things is not like the other! J. Cell Sci. 2019 132 3 jcs220491 10.1242/jcs.220491 30733374
    [Google Scholar]
  8. Yi F. Wang Z. Liu J. Zhang Y. Wang Z. Xu H. Li X. Bai N. Cao L. Song X. Structural maintenance of chromosomes protein 1: Role in genome stability and tumorigenesis. Int. J. Biol. Sci. 2017 13 8 1092 1099 10.7150/ijbs.21206 28924389
    [Google Scholar]
  9. Strunnikov A.V. Jessberger R. Structural maintenance of chromosomes (SMC) proteins. Eur. J. Biochem. 1999 263 1 6 13 10.1046/j.1432‑1327.1999.00509.x 10429180
    [Google Scholar]
  10. Arnold K. Bordoli L. Kopp J. Schwede T. The SWISS-MODEL workspace: A web-based environment for protein structure homology modelling. Bioinformatics 2006 22 2 195 201 10.1093/bioinformatics/bti770 16301204
    [Google Scholar]
  11. Benkert P. Tosatto S.C.E. Schomburg D. QMEAN: A comprehensive scoring function for model quality assessment. Proteins 2008 71 1 261 277 10.1002/prot.21715 17932912
    [Google Scholar]
  12. Laskowski R.A. MacArthur M.W. Moss D.S. Thornton J.M. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Cryst. 1993 26 2 283 291 10.1107/S0021889892009944
    [Google Scholar]
  13. Marchler-Bauer A. Derbyshire M.K. Gonzales N.R. Lu S. Chitsaz F. Geer L.Y. Geer R.C. He J. Gwadz M. Hurwitz D.I. Lanczycki C.J. Lu F. Marchler G.H. Song J.S. Thanki N. Wang Z. Yamashita R.A. Zhang D. Zheng C. Bryant S.H. CDD: NCBI’s conserved domain database. Nucleic Acids Res. 2015 43 D1 D222 D226 10.1093/nar/gku1221 25414356
    [Google Scholar]
  14. Yu C.S. Lin C.J. Hwang J.K. Predicting subcellular localization of proteins for gram‐negative bacteria by support vector machines based on n‐peptide compositions. Protein Sci. 2004 13 5 1402 1406 10.1110/ps.03479604 15096640
    [Google Scholar]
  15. Sharma A. Rana A. Mangtani L. Kalra A. Niraj R.R.K. In silico repurposing of anticancer drug (5-fluorouracil) as an antibacterial agent against Klebsiella pneumoniae . Lett. Drug Des. Discov. 2021 18 12 1178 1186 10.2174/1570180818666210920104935
    [Google Scholar]
  16. Pettersen E.F. Goddard T.D. Huang C.C. Couch G.S. Greenblatt D.M. Meng E.C. Ferrin T.E. UCSF Chimera—A visualization system for exploratory research and analysis. J. Comput. Chem. 2004 25 13 1605 1612 10.1002/jcc.20084 15264254
    [Google Scholar]
  17. Niraj R.R.K. Saini V. Kumar A. QSAR analyses of organophosphates for insecticidal activity and its in-silico validation using molecular docking study. Environ. Toxicol. Pharmacol. 2015 40 3 886 894 10.1016/j.etap.2015.09.021 26492451
    [Google Scholar]
  18. Grosdidier A. Zoete V. Michielin O. SwissDock, a protein-small molecule docking web service based on EADock DSS. Nucleic Acids Res 2011 39 W270 7 10.1093/nar/gkr366
    [Google Scholar]
  19. Grosdidier A. Zoete V. Michielin O. EADock: Docking of small molecules into protein active sites with a multiobjective evolutionary optimization. Proteins 2007 67 4 1010 1025 10.1002/prot.21367 17380512
    [Google Scholar]
  20. Schneidman-Duhovny D. Inbar Y. Nussinov R. Wolfson H.J. PatchDock and SymmDock: Servers for rigid and symmetric docking. Nucleic Acids Res 2005 33 W363 7 10.1093/nar/gki481
    [Google Scholar]
  21. Daina A. Michielin O. Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017 7 1 42717 10.1038/srep42717 28256516
    [Google Scholar]
  22. Piplani S. Saini V. Niraj R.R.K. Pushp A. Kumar A. Homology modelling and molecular docking studies of human placental cadherin protein for its role in teratogenic effects of anti-epileptic drugs. Comput. Biol. Chem. 2016 60 1 8 10.1016/j.compbiolchem.2015.11.003 26625086
    [Google Scholar]
  23. Gupta E. Gupta S.R.R. Niraj R.R.K. Identification of drug and vaccine target in Mycobacterium leprae : A reverse vaccinology approach. Int. J. Pept. Res. Ther. 2020 26 3 1313 1326 10.1007/s10989‑019‑09936‑x
    [Google Scholar]
  24. Piplani S. Singh P.K. Winkler D.A. Petrovsky N. Author correction: In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin. Sci. Rep. 2021 11 1 18610 10.1038/s41598‑021‑98366‑1 34521997
    [Google Scholar]
  25. Szklarczyk D. Franceschini A. Wyder S. Forslund K. Heller D. Huerta-Cepas J. Simonovic M. Roth A. Santos A. Tsafou K.P. Kuhn M. Bork P. Jensen L.J. von Mering C. STRING v10: Protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015 43 D1 D447 D452 10.1093/nar/gku1003 25352553
    [Google Scholar]
  26. Wallace A.C. Laskowski R.A. Thornton J.M. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions. Protein Eng. Des. Sel. 1995 8 2 127 134 10.1093/protein/8.2.127 7630882
    [Google Scholar]
  27. Lipinski C.A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today. Technol. 2004 1 4 337 341 10.1016/j.ddtec.2004.11.007 24981612
    [Google Scholar]
  28. Tian W. Chen C. Lei X. Zhao J. Liang J. CASTp 3.0: Computed atlas of surface topography of proteins. Nucleic Acids Res. 2018 46 W1 W363 W367 10.1093/nar/gky473 29860391
    [Google Scholar]
  29. Sharma A. Sharma A. Rana A. Niraj R.R.K. In-silico repurposing of anticancer drug (5-FU) as an antimicrobial agent against methicillin-resistant Staphylococcus aureus (MRSA). Int. J. Pept. Res. Ther. 2020 26 4 2137 2145 10.1007/s10989‑019‑10010‑9
    [Google Scholar]
  30. Kumari R. Kumar R. Lynn A. g_mmpbsa: A GROMACS tool for high-throughput MM-PBSA calculations. J. Chem. Inf. Model. 2014 54 7 1951 1962 10.1021/ci500020m 24850022
    [Google Scholar]
  31. Gupta S.R.R. Gupta E. Ohri A. Shrivastava S.K. Kachhwaha S. Sharma V. Mishra R.K. Niraj R.R.K. Comparative proteome analysis of Mycobacterium tuberculosis strains - H37Ra, H37Rv, CCDC5180, and CAS/NITR204: A step forward to identify novel drug target. Lett. Drug Des. Discov. 2020 17 11 1422 1431 10.2174/1570180817999200531165148
    [Google Scholar]
  32. Wang M. Tang T. Huang Z. Li R. Ling D. Zhu J. Jiang L. Li J. Li X. Design and synthesis of novel hydroxamic acid derivatives based on quisinostat as promising antimalarial agents with improved safety. Acta Materia Medica 2022 1 2 212 223 10.15212/AMM‑2022‑0007
    [Google Scholar]
  33. Kumar D. Kumar H. Deep A. Kumar R. An updated study of traditional medicines to the era of 1,3,4 oxadiazole derivatives for malaria treatment. Trad Med Res 2023 8 1 5 10.53388/TMR20220614001
    [Google Scholar]
/content/journals/raaidd/10.2174/0127724344313755241021055002
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Deciphering Plasmodium Condensin Core Subunits of Structural Maintenance of Chromosomes 2 (SMC2) as a Putative Drug Target for Antimalarial Drug
Bentham Science Publishers ; https://doi.org/10.2174/0127724344313755241021055002
/content/journals/raaidd/10.2174/0127724344313755241021055002
/content/journals/raaidd/10.2174/0127724344313755241021055002
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  • Article Type:     Research Article
Keywords: Malaria ; in-silico ; structural maintenance of chromosomes 2 (SMC2) ; codensin ; drug ; plasmodium

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