Aminocoumarins; Protein Subunits; 8L70Q75FXE (Adenosine Triphosphate); EC 5.99.1.3 (DNA Gyrase); PCH9QZ1IIH (coumermycin); Adenosine Triphosphate/chemistry/metabolism; Aminocoumarins/chemistry/metabolism; Binding Sites; DNA Gyrase/chemistry/metabolism; Dimerization; Escherichia coli/enzymology; Hydrogen Bonding; Molecular Dynamics Simulation; Protein Structure, Quaternary; Protein Subunits/chemistry/metabolism; Thermus thermophilus/enzymology
Abstract :
[en] Coumermycin A1 is a natural aminocoumarin that inhibits bacterial DNA gyrase, a member of the GHKL proteins superfamily. We report here the first cocrystal structures of gyrase B bound to coumermycin A1, revealing that one coumermycin A1 molecule traps simultaneously two ATP-binding sites. The inhibited dimers from different species adopt distinct sequence-dependent conformations, alternative to the ATP-bound form. These structures provide a basis for the rational development of coumermycin A1 derivatives for antibiotherapy and biotechnology applications.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vanden Broeck, Arnaud ; Integrated Structural Biology Department, IGBMC, UMR7104 CNRS, U1258 Inserm, University of Strasbourg, Illkirch 67404 , France.
McEwen, Alastair G; Integrated Structural Biology Department, IGBMC, UMR7104 CNRS, U1258 Inserm, University of Strasbourg, Illkirch 67404 , France.
Chebaro, Yassmine; Integrated Structural Biology Department, IGBMC, UMR7104 CNRS, U1258 Inserm, University of Strasbourg, Illkirch 67404 , France.
Potier, Noëlle; Laboratoire de Spectrométrie de Masse des Interactions et des Systèmes, UMR 7140 CNRS, University of Strasbourg, Strasbourg 67000 , France.
Lamour, Valérie ; Integrated Structural Biology Department, IGBMC, UMR7104 CNRS, U1258 Inserm, University of Strasbourg, Illkirch 67404 , France. ; Hôpitaux Universitaires de Strasbourg , Strasbourg 67000 , France.
Language :
English
Title :
Structural Basis for DNA Gyrase Interaction with Coumermycin A1.
Collin, F.; Karkare, S.; Maxwell, A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl. Microbiol. Biotechnol. 2011, 92, 479-497, 10.1007/s00253-011-3557-z
Bush, N. G.; Evans-Roberts, K.; Maxwell, A. DNA topoisomerases. EcoSal Plus 2015, 6, 6, 10.1128/ecosalplus.ESP-0010-2014
Lamour, V.; Hoermann, L.; Jeltsch, J. M.; Oudet, P.; Moras, D. An open conformation of the Thermus thermophilus gyrase B ATP-binding domain. J. Biol. Chem. 2002, 277, 18947-18953, 10.1074/jbc.M111740200
Lafitte, D.; Lamour, V.; Tsvetkov, P. O.; Makarov, A. A.; Klich, M.; Deprez, P.; Moras, D.; Briand, C.; Gilli, R. DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5′-methyl group of the noviose. Biochemistry 2002, 41, 7217-7223, 10.1021/bi0159837
Tsai, F. T.; Singh, O. M.; Skarzynski, T.; Wonacott, A. J.; Weston, S.; Tucker, A.; Pauptit, R. A.; Breeze, A. L.; Poyser, J. P.; O'Brien, R.; Ladbury, J. E.; Wigley, D. B. The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins: Struct., Funct., Genet. 1997, 28, 41-52, 10.1002/(SICI)1097-0134(199705)28:1<41::AID-PROT4>3.0.CO;2-M
Lewis, R. J.; Singh, O. M.; Smith, C. V.; Skarzynski, T.; Maxwell, A.; Wonacott, A. J.; Wigley, D. B. The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography. EMBO J. 1996, 15, 1412-1420, 10.1002/j.1460-2075.1996.tb00483.x
Ali, J. A.; Jackson, A. P.; Howells, A. J.; Maxwell, A. The 43-kilodalton N-terminal fragment of the DNA gyrase B protein hydrolyzes ATP and binds coumarin drugs. Biochemistry 1993, 32, 2717-2724, 10.1021/bi00061a033
Alt, S.; Mitchenall, L. A.; Maxwell, A.; Heide, L. Inhibition of DNA gyrase and DNA topoisomerase IV of Staphylococcus aureus and Escherichia coli by aminocoumarin antibiotics. J. Antimicrob. Chemother. 2011, 66, 2061-2069, 10.1093/jac/dkr247
Gormley, N. A.; Orphanides, G.; Meyer, A.; Cullis, P. M.; Maxwell, A. The interaction of coumarin antibiotics with fragments of DNA gyrase B protein. Biochemistry 1996, 35, 5083-5092, 10.1021/bi952888n
Gellert, M.; O'Dea, M. H.; Itoh, T.; Tomizawa, J. Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase. Proc. Natl. Acad. Sci. U. S. A. 1976, 73, 4474-4478, 10.1073/pnas.73.12.4474
Hooper, D. C.; Wolfson, J. S.; McHugh, G. L.; Winters, M. B.; Swartz, M. N. Effects of novobiocin, coumermycin A1, clorobiocin, and their analogs on Escherichia coli DNA gyrase and bacterial growth. Antimicrob. Agents Chemother. 1982, 22, 662-671, 10.1128/AAC.22.4.662
del Castillo, I.; Vizan, J. L.; Rodriguez-Sainz, M. C.; Moreno, F. An unusual mechanism for resistance to the antibiotic coumermycin A1. Proc. Natl. Acad. Sci. U. S. A. 1991, 88, 8860-8864, 10.1073/pnas.88.19.8860
Samuels, D. S.; Garon, C. F. Coumermycin A1 inhibits growth and induces relaxation of supercoiled plasmids in Borrelia burgdorferi the Lyme disease agent. Antimicrob. Agents Chemother. 1993, 37, 46-50, 10.1128/AAC.37.1.46
Fedorko, J.; Katz, S.; Allnoch, H. In vitro activity of coumermycin A1. Appl. Microbiol. 1969, 18, 869-873
Hooper, D. C.; Jacoby, G. A. Mechanisms of drug resistance: quinolone resistance. Ann. N. Y. Acad. Sci. 2015, 1354, 12-31, 10.1111/nyas.12830
Hong, D. S.; Banerji, U.; Tavana, B.; George, G. C.; Aaron, J.; Kurzrock, R. Targeting the molecular chaperone heat shock protein 90 (Hsp90): lessons learned and future directions. Cancer Treat. Rev. 2013, 39, 375-387, 10.1016/j.ctrv.2012.10.001
Chen, N. Y.; Zhou, L.; Gane, P. J.; Opp, S.; Ball, N. J.; Nicastro, G.; Zufferey, M.; Buffone, C.; Luban, J.; Selwood, D.; Diaz-Griffero, F.; Taylor, I.; Fassati, A. HIV-1 capsid is involved in post-nuclear entry steps. Retrovirology 2016, 13, 28, 10.1186/s12977-016-0262-0
Vozzolo, L.; Loh, B.; Gane, P. J.; Tribak, M.; Zhou, L.; Anderson, I.; Nyakatura, E.; Jenner, R. G.; Selwood, D.; Fassati, A. Gyrase B inhibitor impairs HIV-1 replication by targeting Hsp90 and the capsid protein. J. Biol. Chem. 2010, 285, 39314-39328, 10.1074/jbc.M110.155275
Yu, X. M.; Shen, G.; Neckers, L.; Blake, H.; Holzbeierlein, J.; Cronk, B.; Blagg, B. S. Hsp90 inhibitors identified from a library of novobiocin analogues. J. Am. Chem. Soc. 2005, 127, 12778-12779, 10.1021/ja0535864
Wang, Z. X.; Li, S. M.; Heide, L. Identification of the coumermycin A1 biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489. Antimicrob. Agents Chemother. 2000, 44, 3040-3048, 10.1128/AAC.44.11.3040-3048.2000
Steffensky, M.; Muhlenweg, A.; Wang, Z. X.; Li, S. M.; Heide, L. Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891. Antimicrob. Agents Chemother. 2000, 44, 1214-1222, 10.1128/AAC.44.5.1214-1222.2000
Heide, L. The aminocoumarins: biosynthesis and biology. Nat. Prod. Rep. 2009, 26, 1241-1250, 10.1039/b808333a
Wolpert, M.; Heide, L.; Kammerer, B.; Gust, B. Assembly and heterologous expression of the coumermycin A1 gene cluster and production of new derivatives by genetic engineering. ChemBioChem 2008, 9, 603-612, 10.1002/cbic.200700483
Rutkowska, A.; Schultz, C. Protein tango: the toolbox to capture interacting partners. Angew. Chem., Int. Ed. 2012, 51, 8166-8176, 10.1002/anie.201201717
Farrar, M. A.; Alberola-lla, J.; Perlmutter, R. M. Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization. Nature 1996, 383, 178-1781, 10.1038/383178a0
Ehrbar, M.; Schoenmakers, R.; Christen, E. H.; Fussenegger, M.; Weber, W. Drug-sensing hydrogels for the inducible release of biopharmaceuticals. Nat. Mater. 2008, 7, 800-804, 10.1038/nmat2250
White, S. D.; Conwell, K.; Langland, J. O.; Jacobs, B. L. Use of a negative selectable marker for rapid selection of recombinant vaccinia virus. BioTechniques 2011, 50, 303-309, 10.2144/000113667
Brino, L.; Urzhumtsev, A.; Mousli, M.; Bronner, C.; Mitschler, A.; Oudet, P.; Moras, D. Dimerization of Escherichia coli DNA-gyrase B provides a structural mechanism for activating the ATPase catalytic center. J. Biol. Chem. 2000, 275, 9468-9475, 10.1074/jbc.275.13.9468
Confreres, A.; Maxwell, A. gyrB mutations which confer coumarin resistance also affect DNA supercoiling and ATP hydrolysis by Escherichia coli DNA gyrase. Mol. Microbiol. 1992, 6, 1617-1624, 10.1111/j.1365-2958.1992.tb00886.x
Franke, D.; Svergun, D. I. DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering. J. Appl. Crystallogr. 2009, 42, 342-346, 10.1107/S0021889809000338
Phillips, J. W.; Goetz, M. A.; Smith, S. K.; Zink, D. L.; Polishook, J.; Onishi, R.; Salowe, S.; Wiltsie, J.; Allocco, J.; Sigmund, J.; Dorso, K.; Lee, S.; Skwish, S.; de la Cruz, M.; Martin, J.; Vicente, F.; Genilloud, O.; Lu, J.; Painter, R. E.; Young, K.; Overbye, K.; Donald, R. G.; Singh, S. B. Discovery of kibdelomycin, a potent new class of bacterial type II topoisomerase inhibitor by chemical-genetic profiling in Staphylococcus aureus. Chem. Biol. 2011, 18, 955-965, 10.1016/j.chembiol.2011.06.011
Dutta, R.; Inouye, M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci. 2000, 25, 24-28, 10.1016/S0968-0004(99)01503-0
Burlison, J. A.; Neckers, L.; Smith, A. B.; Maxwell, A.; Blagg, B. S. Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90. J. Am. Chem. Soc. 2006, 128, 15529-15536, 10.1021/ja065793p
Cele, F. N.; Kumalo, H.; Soliman, M. E. Mechanism of inhibition of Hsp90 dimerization by gyrase B inhibitor coumermycin A1 (C-A1) revealed by molecular dynamics simulations and thermodynamic calculations. Cell Biochem. Biophys. 2016, 74, 353-363, 10.1007/s12013-016-0743-8
Kusuma, B. R.; Peterson, L. B.; Zhao, H.; Vielhauer, G.; Holzbeierlein, J.; Blagg, B. S. Targeting the heat shock protein 90 dimer with dimeric inhibitors. J. Med. Chem. 2011, 54, 6234-6253, 10.1021/jm200553w
Allan, R. K.; Mok, D.; Ward, B. K.; Ratajczak, T. Modulation of chaperone function and cochaperone interaction by novobiocin in the C-terminal domain of Hsp90: evidence that coumarin antibiotics disrupt Hsp90 dimerization. J. Biol. Chem. 2006, 281, 7161-7171, 10.1074/jbc.M512406200
Burlison, J. A.; Blagg, B. S. Synthesis and evaluation of coumermycin A1 analogues that inhibit the Hsp90 protein folding machinery. Org. Lett. 2006, 8, 4855-4858, 10.1021/ol061918j
Byrd, K. M.; Subramanian, C.; Sanchez, J.; Motiwala, H. F.; Liu, W.; Cohen, M. S.; Holzbeierlein, J.; Blagg, B. S. Synthesis and biological evaluation of novobiocin core analogues as Hsp90 inhibitors. Chem.-Eur. J. 2016, 22, 6921-6931, 10.1002/chem.201504955
