Artículo

Bidon-Chanal, A.; Martí, M.A.; Crespo, A.; Milani, M.; Orozco, M.; Bolognesi, M.; Luque, F.J.; Estrin, D.A. "Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N" (2006) Proteins: Structure, Function and Genetics. 64(2):457-464
La versión final de este artículo es de uso interno de la institución.
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Mycobacterium tuberculosis, the causative agent of human tuberculosis, is forced into latency by nitric oxide produced by macrophages during infection. In response to nitrosative stress M. tuberculosis has evolved a defense mechanism that relies on the oxygenated form of "truncated hemoglobin" N (trHbN), formally acting as NO-dioxygenase, yielding the harmless nitrate ion. X-ray crystal structures have shown that trHbN hosts a two-branched protein matrix tunnel system, proposed to control diatomic ligand migration to the heme, as the rate-limiting step in NO conversion to nitrate. Extended molecular dynamics simulations (0.1 μs), employed here to characterize the factors controlling diatomic ligand diffusion through the apolar tunnel system, suggest that O2 migration in deoxy-trHbN is restricted to a short branch of the tunnel, and that O2 binding to the heme drives conformational and dynamical fluctuations promoting NO migration through the long tunnel branch. The simulation results suggest that trHbN has evolved a dual-path mechanism for migration of O2 and NO to the heme, to achieve the most efficient NO detoxification. © 2006 Wiley-Liss, Inc.

Registro:

Documento: Artículo
Título:Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
Autor:Bidon-Chanal, A.; Martí, M.A.; Crespo, A.; Milani, M.; Orozco, M.; Bolognesi, M.; Luque, F.J.; Estrin, D.A.
Filiación:Departament de Fisicoquímica, Facultat de Farmacia, Universität de Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain
Departamento de Quimica Inorganica, Analitica y Quimica Fisica/INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EHA, Argentina
Department of Biomolecular Sciences and Biotechnology, CNR-INFM, University of Milano, Milano, Italy
Departament de Bioquímica i Biologia Molecular, Facultat de Química, Universitat de Barcelona, Martí i Franqués 1, 08028 Barcelona, Spain
Unidad de Modelización Molecular y Bioinformática, Parc Científic de Barcelona, Josep Samitier 1-6, 08028 Barcelona, Spain
Span and Computacional Biology Program, Barcelona Supercomputing Center, Edificio Nexus II, Barcelona 08028, Spain
University of Buenos Aires, Department of Chemistry, Ciudad Universitaria, Buenos Aires, C1428EHA, Argentina
University of Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain
Palabras clave:Ligand migration; M. tuberculosis; Molecular dynamics; Nitric oxide; deoxy truncated hemoglobin n; dioxygenase; heme; hemoglobin; ligand; nitrate; nitric oxide; oxygen; truncated hemoglobin n; unclassified drug; article; bioinformatics; conformational transition; crystal structure; defense mechanism; diffusion; latent period; macrophage; molecular dynamics; Mycobacterium tuberculosis; nitrosation; nonhuman; oxygen affinity; priority journal; protein conformation; protein function; simulation; structure analysis; X ray crystallography; Mycobacterium tuberculosis
Año:2006
Volumen:64
Número:2
Página de inicio:457
Página de fin:464
DOI: http://dx.doi.org/10.1002/prot.21004
Título revista:Proteins: Structure, Function and Genetics
Título revista abreviado:Proteins Struct. Funct. Genet.
ISSN:08873585
CODEN:PSFGE
CAS:dioxygenase, 37292-90-3; heme, 14875-96-8; hemoglobin, 9008-02-0; nitrate, 14797-55-8; nitric oxide, 10102-43-9; oxygen, 7782-44-7
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08873585_v64_n2_p457_BidonChanal

Referencias:

  • Bloom, B.R., (1994) Tuberculosis: Pathogenesis, Protection and Control, , Washington, DC: ASM Press
  • MacMicking, J.D., North, R.J., LaCourse, R., Mudgett, J.S., Shah, S.K., Nathan, C.F., Identification of nitric oxide synthase as a protective locus against tuberculosis (1997) Proc Natl Acad Sci USA, 94, pp. 5243-5248
  • Quellet, H., Quellet, Y., Richard, C., Labarre, M., Wittenberg, B., Wittenberg, J., Guertin, M., Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide (2002) Proc Natl Acad Sci USA, 99, pp. 5902-5907
  • Couture, M., Yeh, S.R., Wittenberg, B.A., Wittenberg, J.B., Ouellet, Y., Rousseau, D.L., Guertin, M., A cooperative oxygen-binding hemoglobin from Mycobacterium tuberculosis (1999) Proc Natl Acad Sci USA, 96, pp. 11223-11228
  • Moens, L., Globins in nonvertebrate species: Dispersal by horizontal gene transfer and evolution of the structure-function relationships (1996) Mol Biol Evol, 13, pp. 324-333
  • Pesce, A., Couture, M., Dewilde, S., Guertin, M., Yamauchi, K., Ascenzi, P., Moens, L., Bolognesi, M., A novel two-over-two alpha-helical sandwich fold is characteristic of the truncated hemoglobin family (2000) EMBO J, 19, pp. 2424-2434
  • Milani, M., Pesce, A., Nardini, M., Oellet, H., Ouellet, Y., Dewilde, S., Bocedi, A., Bolognesi, M., Structural bases for heme binding and diatomic ligand recognition in truncated hemoglobins (2005) J Inorg Biochem, 99, pp. 97-109
  • Milani, M., Pesce, A., Ouellet, Y., Ascenzi, P., Guertin, M., Bolognesi, M., Mycobacterium tuberculosis hemoglobin N displays a protein tunnel suited for O2 diffusion to the heme (2001) EMBO J, 20, pp. 3902-3909
  • Milani, M., Pesce, A., Ouellet, Y., Dewilde, S., Friedman, J.M., Ascenzi, P., Guertin, M., Bolognesi, M., Heme-ligand tunneling in group I truncated hemoglobins (2004) J Biol Chem, 279, pp. 21520-21525
  • Samuni, U., Dantsker, D., Ray, A., Wittenberg, J.B., Wittenberg, B.A., Dewilde, S., Moens, L., Friedman, J.M., Kinetic modulation in carbonmonoxy derivatives of truncated hemoglobins: The role of distal heme pocket residues and extended apolar tunnel (2003) J Biol Chem, 278, pp. 27241-27250
  • Dantsker, D., Samuni, U., Ouellet, Y., Wittenberg, B.A., Wittenberg, J.B., Milani, M., Bolognesi, M., Friedman, J.M., Viscosity-dependent relaxation significantly modulates the kinetics of CO recombination in the truncated hemoglobin TrHbN from Mycobacterium tuberculosis (2004) J Biol Chem, 279, pp. 38844-38853
  • Crespo, A., Martí, M.A., Kalko, S.G., Morreale, A., Orozco, M., Gelpi, J.L., Luque, F.J., Estrin, D.A., Theoretical study of the truncated hemoglobin HbN: Exploring the molecular basis of the NO detoxification mechanism (2005) J Am Chem Soc, 127, pp. 4433-4444
  • Schotte, F., Lim, M., Jackson, T.A., Smirnov, A.V., Soman, J., Olson, J.S., Phillips Jr., G.N., Anfinrud, P.A., Watching a protein as it function with 150 ps time resolved X-ray crystallography (2003) Science, 300, pp. 1944-1947
  • Chu, K., Vojtchovský, J., McMahon, B.H., Sweet, R.M., Berendzen, J., Schlichting, I., Structure of a ligand binding intermediate in wild type carbonmonoxy myoglobin (2000) Nature, 403, pp. 921-923
  • Case, D.A., Karplus, M., Dynamics of ligand binding to heme proteins (1979) J Mol Biol, 132, pp. 343-368
  • Bossa, C., Anselmi, M., Roccatano, D., Amadei, A., Vallone, B., Brunori, M., Di Nola, A., Extended molecular dynamics simulation of the carbon monoxide migration in sperm whale myoglobin (2004) Biophys J, 86, pp. 3855-3862
  • Nutt, D.R., Meuwly, M., CO migration in native and mutant myoglobin: Atomistic simulations for the understanding of protein function (2004) Proc Natl Acad Sci USA, 101, pp. 5998-6002
  • Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W., Klein, M.L., Comparison of sample potential functions for simulating liquid water (1983) J Chem Phys, 79, pp. 926-935
  • Berendsen, H.J.C., Postma, J.P.M., Van Gunsteren, W.F., Di Nola, A., Haak, J.R., Molecular dynamics with coupling to an external bath (1984) J Chem Phys, 81, pp. 3684-3690
  • Leach, A.R., (2001) Molecular Modelling. 2nd Ed., , Englewood Cliffs, NJ: Prentice Hall
  • Wang, J., Cieplak, P., Kollman, P.A., How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? (2000) J Comput Chem, 21, pp. 1049-1074
  • Pearlman, D.A., Case, D.A., Caldwell, J.W., Ross, W.R., Cheatham III, T.E., Debolt, S., Ferguson, D., Kollman, P., AMBER, a computer program for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to elucidate the structures and energies of molecules (1995) Comp Phys Commun, 91, pp. 1-41
  • Bayly, C.I., Cieplak, P., Cornell, W., Kollman, P.A., A well behaved electrostatic potential based method using charge restraints for deriving atomic charges: The RESP model (1993) J Phys Chem, 97, pp. 10269-10280
  • Jarzynski, C., Non equilibrium equality for free energy differences (1997) Phys Rev Lett, 78, pp. 2690-2693
  • Amadei, A., Linssen, A.B.M., Berendsen, H.J.C., Essential dynamics of proteins (1993) Proteins, 17, pp. 412-415
  • Mukai, M., Ouellet, Y., Guertin, M., Yeh, S.-R., NO binding induced conformational changes in a truncated hemoglobin from Mycobacterium tuberculosis (2004) Biochemistry, 43, pp. 2764-2770
  • Ascenzi, P., Salvati, L., Brunori, M., Does myoglobin protect Trypanosoma cruzi from the antiparasitic effects of nitric oxide? (2001) FEBS Lett, 501, pp. 103-105
  • Eich, R.F., Li, T., Lemon, D.D., Doherty, D.H., Curry, S.R., Aitken, J.F., Mathews, A.J., Olson, J.S., Mechanism of NO-induced oxidation of myoglobin and hemoglobin (1996) Biochemistry, 35, pp. 6976-6983
  • Brunori, M., Giuffrè, A., Nienhaus, K., Ulrich Nienhaus, G., Scandurra, F.M., Vallone, B., Neuroglobin, nitric oxide, and oxygen: Functional pathways and conformational changes (2005) Proc Natl Acad Sci USA, 102, pp. 8483-8488

Citas:

---------- APA ----------
Bidon-Chanal, A., Martí, M.A., Crespo, A., Milani, M., Orozco, M., Bolognesi, M., Luque, F.J.,..., Estrin, D.A. (2006) . Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N. Proteins: Structure, Function and Genetics, 64(2), 457-464.
http://dx.doi.org/10.1002/prot.21004
---------- CHICAGO ----------
Bidon-Chanal, A., Martí, M.A., Crespo, A., Milani, M., Orozco, M., Bolognesi, M., et al. "Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N" . Proteins: Structure, Function and Genetics 64, no. 2 (2006) : 457-464.
http://dx.doi.org/10.1002/prot.21004
---------- MLA ----------
Bidon-Chanal, A., Martí, M.A., Crespo, A., Milani, M., Orozco, M., Bolognesi, M., et al. "Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N" . Proteins: Structure, Function and Genetics, vol. 64, no. 2, 2006, pp. 457-464.
http://dx.doi.org/10.1002/prot.21004
---------- VANCOUVER ----------
Bidon-Chanal, A., Martí, M.A., Crespo, A., Milani, M., Orozco, M., Bolognesi, M., et al. Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N. Proteins Struct. Funct. Genet. 2006;64(2):457-464.
http://dx.doi.org/10.1002/prot.21004