Structures of free and inhibited forms of the L, D-transpeptidase LdtMt1 from Mycobacterium tuberculosis(398 views) Correale S, Ruggiero A, Capparelli R, Pedone E, Berisio R
Keywords: Cell Wall, D-Transpeptidases, Peptidoglycan, Tuberculosis, Antiinfective Agent, Bacterial Protein, Imipenem, Peptidyltransferase, Recombinant Protein, Article, Biosynthesis, Chemistry, Crystallization, Drug Antagonism, Drug Effect, Enzyme Active Site, Enzymology, Genetics, Isolation And Purification, Metabolism, Multidrug Resistant Tuberculosis, Mycobacterium Tuberculosis, Protein Binding, X Ray Crystallography, Anti-Bacterial Agents, Catalytic Domain, X-Ray, Peptidyl Transferases, Multidrug-Resistant, Anti-Bacterial Agents Chemistry, Bacterial Proteins Antagonists, Inhibitors Chemistry Genetics, Imipenem Pharmacology Therapeutic Use, Mycobacterium Tuberculosis Drug Effects Enzymology, Peptidyl Transferases Antagonists, Recombinant Proteins Biosynthesis Chemistry Isolation, Multidrug-Resistant Drug Therapy Enzymology Metabolism,
Affiliations: *** IBB - CNR ***
Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, 80134 Napoli, Italy
Kedrion S.p.A, 80029 S. Antimo (Napoli), Italy
Department of Soil, Plant, Environmental and Animal Production Sciences, School of Biotechnological Sciences, University of Naples 'Federico II', Portici, Italy
Kedrion S. p. A, 80029 S. Antimo (Napoli), Italy
References: Berisio, R., Ciccarelli, L., Squeglia, F., De Simone, A., Vitagliano, L., (2012) Protein Pept. Lett, 19, pp. 1045-105
Betts, J.C., Lukey, P.T., Robb, L.C., McAdam, R.A., Duncan, K., (2002) Mol. Microbiol, 43, pp. 717-731
Biarrotte-Sorin, S., Hugonnet, J.-E., Delfosse, V., Mainardi, J.-L., Gutmann, L., Arthur, M., Mayer, C., (2006) J. Mol. Biol, 359, pp. 533-538
Bö Th, D., Steiner, E.M., Stadler, D., Lindqvist, Y., Schnell, R., Schneider, G., (2013) Acta Cryst. D, 69, pp. 432-441
Chim, N., (2011) Tuberculosis, 91, pp. 155-172
Correale, S., Ruggiero, A., Pedone, E., Berisio, R., (2013) Acta Cryst. F, 69, pp. 253-256
Dubée, V., Arthur, M., Fief, H., Triboulet, S., Mainardi, J.-L., Gutmann, L., Sollogoub, M., Hugonnet, J.-E., (2012) Antimicrob. Agents Chemother, 56, pp. 3409-3412
Dubée, V., Triboulet, S., Mainardi, J.-L., Ethève-Quelquejeu, M., Gutmann, L., Marie, A., Dubost, L., Arthur, M., (2012) Antimicrob. Agents Chemother, 56, pp. 4189-4195
England, K., Boshoff, H.I., Arora, K., Weiner, D., Dayao, E., Schimel, D., Via, L.E., Barry III, C.E., (2012) Antimicrob. Agents Chemother, 56, pp. 3384-3387
Erdemli, S.B., Gupta, R., Bishaiw, R., Lamichhane, G., Amzel, L.M., Bianchet, M.A., (2012) Structure, 20, pp. 2103-2115
Magnet, S., Arbeloa, A., Mainardi, J.-L., Hugonnet, J.-E., Fourgeaud, M., Dubost, L., Marie, A., Arthur, M., (2007) J. Biol. Chem, 282, pp. 13151-13159
Mainardi, J.-L., Fourgeaud, M., Hugonnet, J.-E., Dubost, L., Brouard, J.-P., Ouazzani, J., Rice, L.B., Arthur, M., (2005) J. Biol. Chem, 280, pp. 38146-38152
Mukamolova, G.V., Kaprelyants, A.S., Young, D.I., Young, M., Kell, D.B., (1998) Proc. Natl Acad. Sci. USA, 95, pp. 8916-8921
Mukamolova, G.V., Yanopolskaya, N.D., Kell, D.B., Kaprelyants, A.S., (1998) Antonie Van Leeuwenhoek, 73, pp. 237-243
Murillo, A.C., (2007) Infect. Disord. Drug Targets, 7, pp. 127-139
Otwinowski, Z., Minor, W., (1997) Methods Enzymol, 276, pp. 307-326
Rostkowski, M., Olsson, M.H., Søndergaard, C.R., Jensen, J.H., (2011) BMC Struct. Biol, 11, p. 6
Ruggiero, A., De Simone, P., Smaldone, G., Squeglia, F., Berisio, R., (2012) Curr. Protein Pept. Sci, 13, pp. 756-766
Ruggiero, A., Marasco, D., Squeglia, F., Soldini, S., Pedone, E., Pedone, C., Berisio, R., (2010) Structure, 18, pp. 1184-1190
Ruggiero, A., Marchant, J., Squeglia, F., Makarov, V., De Simone, A., Berisio, R., (2013) J. Biomol. Struct. Dyn, 31, pp. 195-205
Ruggiero, A., Squeglia, F., Marasco, D., Marchetti, R., Molinaro, A., Berisio, R., (2011) Biochem. J, 435, pp. 33-41
Ruggiero, A., Tizzano, B., Pedone, E., Pedone, C., Wilmanns, M., Berisio, R., (2009) J. Mol. Biol, 385, pp. 153-162
Squeglia, F., Marchetti, R., Ruggiero, A., Lanzetta, R., Marasco, D., Dworkin, J., Petoukhov, M., Silipo, A., (2011) J. Am. Chem. Soc, 133, pp. 20676-20679
Terwilliger, T., (2004) J. Synchrotron Rad, 11, pp. 49-52
Trefzer, C., Skovierová, H., Buroni, S., Bobovská, A., Nenci, S., Molteni, E., Pojer, F., Johnsson, K., (2012) J. Am. Chem. Soc, 134, pp. 912-915
Winn, M.D., (2011) Acta Cryst. D, 67, pp. 235-242
Betts, J. C., Lukey, P. T., Robb, L. C., McAdam, R. A., Duncan, K., (2002) Mol. Microbiol, 43, pp. 717-731
B Th, D., Steiner, E. M., Stadler, D., Lindqvist, Y., Schnell, R., Schneider, G., (2013) Acta Cryst. D, 69, pp. 432-441
Dub e, V., Arthur, M., Fief, H., Triboulet, S., Mainardi, J. -L., Gutmann, L., Sollogoub, M., Hugonnet, J. -E., (2012) Antimicrob. Agents Chemother, 56, pp. 3409-3412
Dub e, V., Triboulet, S., Mainardi, J. -L., Eth ve-Quelquejeu, M., Gutmann, L., Marie, A., Dubost, L., Arthur, M., (2012) Antimicrob. Agents Chemother, 56, pp. 4189-4195
Erdemli, S. B., Gupta, R., Bishaiw, R., Lamichhane, G., Amzel, L. M., Bianchet, M. A., (2012) Structure, 20, pp. 2103-2115
Finn, R. D., Mistry, J., Schuster-B Ckler, B., Griffiths-Jones, S., Hollich, V., Lassmann, T., Moxon, S., Bateman, A., (2006) Nucleic Acids Res, 34, pp. D247-D251
Hugonnet, J. -E., Blanchard, J. S., (2007) Biochemistry, 46, pp. 11998-12004
Hugonnet, J. -E., Tremblay, L. W., Boshoff, H. I., Barry III, C. H., Blanchard, J. S., (2009) Science, 323, pp. 1215-1218
Kaprelyants, A. S., Mukamolova, G. V., Ruggiero, A., Makarov, V. A., Demina, G. R., Shleeva, M. O., Potapov, V. D., Shramko, P. A., (2012) Protein Pept. Lett, 19, pp. 1026-1034
Kim, H. S., Kim, J., Im, H. N., Yoon, J. Y., An, D. R., Yoon, H. J., Kim, J. Y., Suh, S. W., (2013) Acta Cryst. D, 69, pp. 420-431
Kluge, A. F., Petter, R. C., (2010) Curr. Opin. Chem. Biol, 14, pp. 421-427
Laskowski, R. A., Rullmann, J. A. C., MacArthur, M. W., Kaptein, R., Thornton, J. M., (1996) J. Biomol. NMR, 8, pp. 477-486
Lecoq, L., Dub e, V., Triboulet, S., Bougault, C., Hugonnet, J. -E., Arthur, M., Simorre, J. -P., (2013) ACS Chem. Biol, , doi: 10. 1021/cb4001603
Mainardi, J. -L., Fourgeaud, M., Hugonnet, J. -E., Dubost, L., Brouard, J. -P., Ouazzani, J., Rice, L. B., Arthur, M., (2005) J. Biol. Chem, 280, pp. 38146-38152
Mukamolova, G. V., Kaprelyants, A. S., Young, D. I., Young, M., Kell, D. B., (1998) Proc. Natl Acad. Sci. USA, 95, pp. 8916-8921
Murillo, A. C., (2007) Infect. Disord. Drug Targets, 7, pp. 127-139
Winn, M. D., (2011) Acta Cryst. D, 67, pp. 235-242
Structures of free and inhibited forms of the L, D-transpeptidase LdtMt1 from Mycobacterium tuberculosis
The modelling of peptidoglycan is responsible for key cellular processes in Mycobacterium tuberculosis such as cell growth, division and resuscitation from dormancy. The structure of M. tuberculosis peptidoglycan is atypical since it contains a majority of 3,3 cross-links synthesized by L,D-transpeptidases that replace the 4,3 cross-links formed by the D,D-transpeptidase activity of classical penicillin-binding proteins. Carbapenems inactivate these L,D-transpeptidases and in combination with clavulanic acid are bactericidal against extensively drug-resistant M. tuberculosis. Here, crystal structures of the L,D-transpeptidase LdtMt1 from M. tuberculosis in a ligand-free form and in complex with the carbapenem imipenem are reported. Elucidation of the structural features of LdtMt1 unveils analogies and differences between the two key transpeptidases of M. tuberculosis: LdtMt1 and LdtMt2. In addition, the structure of imipenem-inactivated LdtMt1 provides a detailed structural view of the interactions between a carbapenem drug and LdtMt1. By providing the key interactions in the binding of carbapenem to LdtMt1, this work will facilitate structure-guided discovery of L,D-transpeptidase inhibitors as novel antitubercular agents against drug-resistant M. tuberculosis.
Structures of free and inhibited forms of the L, D-transpeptidase LdtMt1 from Mycobacterium tuberculosis