Molecular modelling of FtsZ proteins based on their homology in Escherichia coli and Mycobacterium tuberculosis as the key stage of rational design of new antituberculous compounds


  • Oleh Demchuk
  • Pavel Karpov
  • Peter Raspor
  • Yaroslav Blume



FtsZ, Escherichia coli, Mycobacterium tuberculosis, 3D-structure modelling and verification, in silico


The analysis of the quality of X-ray structures from Mycobacterium tuberculosis FtsZ proteins, which are deposited in the ProteinDataBank, gave a possibility to select a 2Q1Y (Chain A) structure as a template for future in silico research. Also several spatial models of FtsZ protein from Escherichia coli were reconstructed with on-line servers »Swiss-Model Workspace« and I-Tasser, than the most appropriate structure was selected. Basing on complex bioinformatic study, the model, which was rebuilt by SwissModel server from 2Q1Y (chain A) template, was supposed as the most significant.


Arnold, K., Bordoli, L., Kopp, J., Schwede, T., 2006. The »SWISS-MODEL Workspace«: A web-based environment for protein structure homology modelling. Bioinformatics, 22, 195–201. DOI:

Benkert, P., Biasini, M., Schwede, T., 2011. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics, 27, (3), 343–350. DOI:

Benkert, P., Schwede, T., Tosatto, S.C.E., 2009. QMEANclust: Estimation of protein model quality bycombining a composite scoring function with structural density information. BMC Struct. Biol., 9 (35), doi:10.1186/1472-6807-9-35. DOI:

Berman, H.M., Henrick, K., Nakamura, H., 2003. Announcing the worldwide Protein Data Bank. Nat. Struct. Biol., 10 (12), p. 980. DOI:

Chen, V.B., Arendall, W.B. III, Headd, J.J., Keedy, D.A., Immormino, R.M., Kapral, G.J., Murray, L.W., Richardson, J.S., Richardson, D.C., 2010. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D: Biol. Crystallogr., D66 (1), 12–21. DOI:

Cole, S.T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C.M., Harris, D.E., Gordon, S.V., Eiglmeier, K., Gas, S., Barry, C.E. III, Tekaia, F., Badcock, K., Basham, D., Brown, D., Chillingworth, T., Connor, R., Davies, R.M., Devlin, K., Barrell, B.G., 1998. Deciphering the biology of M. tuberculosis from the complete genome sequence, Nature, 393, 537–544. DOI:

Cordell, S.C., Robinson, E.J.H., Löwe, J., 2003. Crystal structure of the SOS cell division inhibitor SulA and in complex with FtsZ. Proc. Natl. Acad. Sci. USA, 100 (13), 7889–7894. DOI:

Demchuk, O.N., Blume, Ya.B., 2005. Phylogenetic tree of bacterial and eucaryotic FtsZ-proteins created according to the homology of their primary sequences, Cytol. Genetics, 39 (4), 3–12.

Erickson, H.P., 1998. Atomic structures of tubulin and FtsZ, Trends Cell Biol., 8, 133–137. DOI:

Fleischmann, R.D., Alland, D., Eisen, J.A., Carpenter, L., White, O., Peterson, J.D., DeBoy, R.T., Dodson, R.J., Gwinn, M.L., Haft, D.H., Hickey, E.K., Kolonay, J.F., Nelson, W.C., Umayam, L.A., Ermolaeva, M.D., Salzberg, S.L., Delcher, A., Utterback, T.R., Fraser, C.M., 2002. Whole-genome

comparison of M. tuberculosis clinical and laboratory strains. J. Bacteriol., 184, 5479–5490.

Gu, J., Bourne, P.E., 2009. Structural Bioinformatics, 2nd ed. John Wiley and Sons, New Jersey, 1035 pр. Guex, N., Peitsch, M.C., 1997. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modelling. Electrophoresis, 18 (15), 2714–2723. DOI:

Haydon, D.J., Stokes, N.R., Ure, R., Galbraith, G., Bennett, J.M., Brown, D.R., Baker, P.J., Barynin, V.V., Rice, D.W., Sedelnikova, S.E., Heal, J.R., Sheridan, J.M., Aiwale, S.T., Chauhan, P.K., Srivastava, A., Taneja, A., Collins, I., Errington, J., Czaplewski, L.G., 2008. An inhibitor of FtsZ

with potent and selective anti-staphylococcal activity. Science, 321, 1673–1675. DOI:

Höltje, H.-D., Sippl, W., Rognan, D., Folkers, G., 2008. Molecular modeling. Basic Principles and Applications, 3rd Ed.. Wiley-VCH, p. 320,

Huang, Q., Kirikae, F., Kirikae, T., Pepe, A., Slayden, R.A., Tonge, P.J., Ojima, I., 2006. Targeting FtsZ for anti-tuberculosis drug discovery: non-cytotoxic taxanes as novel anti-tuberculosis agents. J. Med. Chem., 49 (2), 463–466. DOI:

Jaiswal, R., Beuria, T.K., Mohan, R., Mahajan, S.K., Panda, D., 2007. Totarol inhibits bacterial cytokinesis by perturbing the assembly dynamics of FtsZ. Biochem., 46 (14), 4211–4220. DOI:

Kumar, K., Awasthi, D., Berger, W.T., Tonge, P.J., Slayden, R.A., Ojima, I., 2010. Discovery of anti-TB agents that target the cell-division protein FtsZ. Future Med Chem., 2 (8), 1305–1323. DOI:

Kumar, K., Awasthi, D., Lee, S-Y., Zanardi, I., Ruzsicska, B., Knudson, S., Tonge, P.J., Slayden, R.A., Ojima, I., 2011.Novel trisubstituted benzimidazoles, targeting Mtb FtsZ, as a new class of antitubercular agents. J. Med. Chem., 54, 374–381. DOI:

Läppchen, T., Pinas, V.A., Hartog, A.F., Koomen, G.J., Schaffner-Barbero, C., Andreu, J.M., Trambaiolo, D., Löwe, J., Juhem, A., Popov, A.V., den Blaauwen, T., 2008. Probing FtsZ and tubulin with C8-substituted GTP analogs reveals differences in their nucleotide binding sites. Chem. DOI:

Biol., 15, 189–199.

Larkin, M.A., Blackshields, G., Brown, N.P., Chenna, R., McGettigan, P.A., McWilliam, H., Valentin, F., Wallace, I.M., Wilm, A., Lopez, R., Thompson, J.D., Gibson, T.J., Higgins, D.G., 2007. Clustal W and Clustal X version 2.0. Bioinformatics, 23, 2947–2948. DOI:

Leung, A.K., Lucile White, E., Ross, L.J., Reynolds, R.C., DeVito, J.A., Borhani, D.W., 2004. Structure of M. tuberculosis FtsZ reveals unexpected, G protein-like conformational switches. J. Mol. Biol., 342 (3), 953–970. DOI:

Li, Y., Zhang, Y., 2009. REMO: A new protocol to refine full atomic protein models from C-alpha traces by optimizing hydrogen-bonding networks. Proteins, 76, 665–676. DOI:

Löwe, J., Amos, L.A., 1998. Crystal structure of the bacterial cell-division protein FtsZ. Nature, 391, 203–206. DOI:

Margalit, D.N., Romberg, L., Mets, R.B., Hebert, A.M., Mitchison, T.J., Kirschner, M.W., Chaudhuri, D.R., 2004. Targeting cell division: small-molecule inhibitors of FtsZ GTPase perturb cytokinetic ring assembly and induce bacterial lethality. PNAS., 101, 11821–11826. DOI:

Mosyak, L., Zhang, Y., Glasfeld, E., Haney, S., Stahl, M., Seehra, J., Somers, W.S., 2000. The bacterial cell-division protein ZipA and its interaction with an FtsZ fragment revealed by X-ray crystallography. EMBO J., 19 (13), 3179–3191. DOI:

Nyporko, A.Yu., Blume, Ya.B., 2001. Comparative analysis of the tubulin secondary structure. Biopolym. Сell, 17, (1), 61–69, in Russian. DOI:

Ohashi, Y., Chijiiwa, Y., Suzuki, K., Takahashi, K., Nanamiya, H., Sato, T., Hosoya, Y., Ochi, K., Kawamura, F., 1999. The lethal effect of a benzamide derivative, 3-methoxybenzamide, can be suppressed by mutations within a cell division gene, ftsZ, in Bacillus subtilis. J. Bacteriol., 181 (4), 1348–1351. DOI:

Oliva, M.A., Cordell, S.C., Löwe, J., 2004. Structural insights into FtsZ protofilament formation, Nat. Struct. Mol. Biol., 11 (12), 1243–1250. DOI:

Oliva, M.A., Trambaiolo, D., Löwe, J., 2007. Structural insights into the conformational variability of FtsZ. J. Mol. Biol., 373 (5), 1229–1242. DOI:

Perna, N.T., Plunkett 3rd, G., Burland, V., Mau, B., Glasner, J.D., Rose, D.J., Mayhew, G.F., Evans, P.S., Gregor, J., Kirkpatrick, H.A., Pósfai, G., Hackett, J., Klink, S., Boutin, A., Shao, Y., Miller, L., Grotbeck, E.J., Davis, N.W., Lim, A., Dimalanta, E.T., Potamousis, K.D., Apodaca, J., Anantharaman, T.S., Lin, J., Yen, G., Schwartz, D.C., Welch, R.A., Blattner, F.R., 2001. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7, Nature, 409 (6819), 529–533. DOI:

Raymond, A., Lovell, S., Lorimer, D., Walchli, J., Mixon, M., Wallace, E., Thompkins, K., Archer, K., Burgin, A., Stewart, L., 2009. Combined protein construct and synthetic gene engineering for heterologous protein expression and crystallization using Gene Composer, BMC Biotechnol., 9

(37), doi: 10.1186/1472-6750-9-37. DOI:

Raviglione, M.C., 2000. Issues facing TB control (7). Multiple drug-resistant tuberculosis, Scott. Med. J., 45, (5), 52–55. DOI:

Respicio, L., Nair, P.A., Huang, Q., Anil, B., Tracz, S., Truglio, J.J., Kisker, C., Raleigh, D.P., Ojima, I., Knudson, D.L., Identification of FtsZ polymerization regulatory elements using a M. tuberculosis FtsZ temperature sensitive mutant. To be published, DOI:10.2210/pdb2q1y/pdb DOI:

Roy, A., Kucukural, A., Zhang, Y. 2010. I-TASSER: a unified platform for automated protein structure and function prediction. Nat. Protoc., 5 (4), 725–738. DOI:

Roy, A., Zhang, Y., 2011 COFACTOR: protein-ligand binding site predictions by global structure similarity match and local geometry refinement, – in print. The UniProt Consortium, 2008. The Universal Protein Resource (UniProt). Nucl Acids Res., 36, 190–195. DOI:

Vaughan, S., Wickstead, B., Gull, K., Addinall, S.G., 2004. Molecular evolution of FtsZ protein sequences encoded within the genomes of archaea, bacteria, and eukaryote. J. Mol. Evol., 58 (1), 19–39. DOI:

White, E.L., Ross, L.J., Reynolds, R.C., Seitz, L.E., Moore, G.D., Borhani, D.W., 2000. Slow polymerization of M. tuberculosis FtsZ. J. Bacteriol., 182 (14), 4028–4034. DOI:

White, E.L., Suling, W.J., Ross, L.J., Seitz, L.E., Reynolds, R.C., 2002. 2-alkoxycarbonylaminopyridines: inhibitors of M. tuberculosis FtsZ. J. Antimicrob Chemother., 50 (1), 111–114. DOI:

Wu, S., Zhang, Y., 2007. LOMETS: a local meta-threading-server for protein structure prediction. Nucleic Acids Res., 35, 3375–3382. DOI:

Yu, X.-C., Margolin, W., 1998. Inhibition of assembly of bacterial cell division protein FtsZ by the hydrophobic dye 5,5*-Bis-(8-anilino-1-aphthalenesulfonate). J. Biol. Chem., 273 (17), 10216–10222. DOI:

Zhang, J., Zhang, Y., 2011. High-resolution protein structure refinement using fragment guided molecular dynamics simulations. Structure, in press. Zhang, Y., Kihara, D., Skolnick, J., 2002. Local energy landscape flattening: parallel hyperbolic Monte Carlo sampling of protein folding. Proteins, 48, 192–201. DOI:

Zhang, Y., Skolnick, J., 2004. Scoring function for automated assessment of protein structure template quality. Proteins, 57 (4), 702–710. DOI:

Zhou, H., Zhou, Y., 2002. Distance-scaled, finite ideal-gas reference state improves structurederived potentials of mean force for structure selection and stability prediction. Protein Sci., 11, 2714–2726. DOI:






Original Research Paper

How to Cite

Demchuk, O., Karpov, P., Raspor, P., & Blume, Y. (2011). Molecular modelling of FtsZ proteins based on their homology in Escherichia coli and Mycobacterium tuberculosis as the key stage of rational design of new antituberculous compounds. Acta Biologica Slovenica, 54(2), 15-30.

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