Navegar

Colección

Datos Estadísticas

Artículo

La versión final de este artículo es de uso interno. El editor solo permite incluir en el repositorio el artículo en su versión post-print. Por favor, si usted la posee enviela a
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Formation of protein ligand complexes is a fundamental phenomenon in biochemistry. During the process, significant solvent reorganization is produced along the contact surface and many water molecules strongly bound to the protein's ligand binding site must be displaced. Both the thermodynamics and kinetics of this process are complex and a clear understanding at the microscopic level has been not achieved so far. Special attention has been paid to the structure of water molecules on carbohydrate recognition sites of various proteins, and many studies support the idea that displacement of these water molecules should have a crucial effect on the binding free energy. Molecular dynamics (MD) simulations in explicit water solvent is a very promising approach for this type of studies. Using MD simulations combined with statistical mechanics analysis, thermodynamic properties of these water molecules can be computed and analyzed in a comparative view. Using this idea, we developed a set of analysis tools to link solvation with ligand binding in a key carbohydrate binding protein, human galectin-1 (hGal-1). Specifically, we defined water sites (WS) in terms of the thermodynamic properties of water molecules strongly bound to protein surfaces. In the present work, we selected a group of proteins whose ligand bound complexes have been already structurally characterized in order to extend the analysis of the role of the surface associated water molecules in the ligand binding and recognition process. The selected proteins are concanavalin-A (Con-A), galectin-3 (Gal-3), cyclophilin-A (Cyp-A), and two modules CBM40 and CBM32 of the multimodular bacterial sialidase. Our results show that the probability of finding water molecules inside the WS, p(V), with respect to the bulk density is directly correlated to the likeliness of finding an hydroxyl group of the ligand in the protein-ligand complex. This information can be used to analyze in detail the solvation structure of the carbohydrate recognition domain (CRD) and its relation to the possible protein ligand complexes and suggests addition of OH-containing functional groups to displace water from high p(V) WS to enhance drugs, specially glycomimetic-drugs, protein affinity, and/or specificity. © 2009 American Chemical Society.

Registro:

Documento: Artículo
Título:Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy
Autor:Gauto, D.F.; Di Lella, S.; Guardia, C.M.A.; Estrin, D.A.; Martí, M.A.
Filiación:Departamento de Química Inorgánica, INQUIMAE-CONICET, Universidad de Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
Universidad Nacional de Tucumán, Chacabuco 462, Tucumán, Argentina
Palabras clave:Binding energy; Binding sites; Biochemistry; Carbohydrates; Complexation; Dynamics; Functional groups; Ligands; Molecular dynamics; Molecules; Probability density function; Proteins; Solvation; Solvents; Statistical mechanics; Thermodynamic properties; Analysis tools; Associated water; Binding free energy; Binding proteins; Bulk density; Carbohydrate binding; Carbohydrate recognition; Carbohydrate-recognition domains; Contact surface; Cyclophilin; Explicit water; Galectin-1; Hydroxyl groups; Ligand binding; Ligand structure; Ligand-binding sites; MD simulation; Microscopic levels; Molecular dynamics simulations; Multi-modular; Protein affinity; Protein surface; Protein-ligand complexes; Recognition process; Sialidase; Solvation structure; Solvent environments; Solvent reorganization; Thermodynamics and kinetics; Water molecule; Water analysis
Año:2009
Volumen:113
Número:25
Página de inicio:8717
Página de fin:8724
DOI: http://dx.doi.org/10.1021/jp901196n
Título revista:Journal of Physical Chemistry B
Título revista abreviado:J Phys Chem B
ISSN:15206106
CODEN:JPCBF
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v113_n25_p8717_Gauto

Referencias:

  • Teeter, M.M., (1991) Annu. Rev. Biophys. Biophys. Chem, 20, p. 577
  • Schoenborn, B.P., Garcia, A., Knott, R., (1995) Prog. Biophys. Mol. Biol, 64, p. 105
  • Henchman, R.H., McCammon, J.A., (2002) Protein Sci, 11, p. 2080
  • Tame, J.R.H., Murshudov, G.N., Dodson, E.J., Neil, T.K., Wilkinson, A.J., (1994) Science, 264, p. 1578
  • Sleigh, S.H., Tame, J.R.H., Dodson, E.J., Wilkinson, A.J., (1997) Biochemistry, 36, p. 9747
  • Nasimith, J.H., Field, R.A., (1996) J. Biol. Chem, 271, p. 972
  • Loris, R., Maes, D., Poortmans, F., Wyns, L., Bouckaert, J., (1996) J. Biol. Chem, 271, p. 30614
  • Weisner, S., Kurian, E., Prendergast, F.G., Halle, B., (1999) J. Mol. Biol, 286, p. 233
  • Asensio, J.L., Siebert, H.-C., von der Lieth, C.-W., Laynez, J., Bruix, M., Soedjanaamadja, U.M., Beintema, J.J., Jiménez-Barbero, J., (2000) Proteins: Struct., Funct., Genet, 40, p. 218
  • Clarke, C., Woods, R.J., Gluska, J., Cooper, A., Nutley, M.A., Boons, G., (2001) J. Am. Chem. Soc, 123, p. 12238
  • Chervenak, M.C., Toone, E.J., (1995) Biochemistry, 34, p. 5685
  • Dunitz, J.D., (1994) Science, 264, p. 670
  • Lam, P.Y.S., Jadhav, P.K., Eyermann, C.J., Hodge, C.N., Ru, Y., Bacheler, L.T., Meek, J.L., Erickson-Viitanen, S., (1994) Science, 263, p. 380
  • Watson, K.A., Mitchell, E.P., Johnson, L.N., Son, J.C., Bichard, C.J.F., Orchard, M.G., Fleet, G.W.J., Papageorgioui, A., (1994) Biochemistry, 33, p. 5745
  • Conelly, P.R., Aldape, R.A., Wilson, K.P., (1994) Proc. Natl. Acad. Sci. U.S.A, 91, p. 1964
  • Li, Z., Lazaridis, T., (2005) J. Phys. Chem. B, 109, p. 662
  • Hamelberg, D., McCammon, J.A., (2004) J. Am. Chem. Soc, 126, p. 7683
  • Li, Z., Lazaridis, T., (2006) J. Phys. Chem. B, 110, p. 1464
  • Rabinovich, G.A., Liu, F.T., Hirashima, M., Anderson, A., (2007) Scand. J. Immunol, 66, p. 143
  • Li, Z., Lazaridis, T., (2003) J. Am. Chem. Soc, 125, p. 6636
  • Di Lella, S., Marti, M.A., Alvarez, R.M.S., Estrin, D.A., Díaz Ricci, J.C., (2007) J. Phys. Chem. B, 111, p. 7360
  • Mayo, K.H., (2008) Drugs, 11, p. 1
  • Sörme, P., Arnoux, P., Kahl-Knutsson, B., Leffler, H., Rini, J.M., Nilsson, U.J., (2005) J. Am. Chem. Soc, 127, p. 1737
  • Ö berg, C. T.; Leffler, H.; Nilsson, U. J. J. Med. Chem. 2008, 51, 2297; Tejler, J., Skogman, F., Leffler, H., Nilsson, U.J., (2007) Carbohydr. Res, 342, p. 1869
  • Abel, R., Young, T., Farid, R., Berne, B.J., Friesner, R.A., (2008) J. Am. Chem. Soc, 130, p. 2817
  • Cooper, D.N.W., Barondes, S.H., (1999) Glycobiology, 9, p. 979
  • Leffler, H., (1997) Trends Glycosci. Glycotechnol, 9, p. 9
  • Lopez-Lucendo, M.F., Solis, D., Andre, S., Hirabayashi, J., Kasai, K., Kaltner, H., Gabius, H.J., Romero, A., (2004) J. Mol. Biol, 343, p. 957
  • Bianchet, M., Ahmed, H., Vasta, G., Amzel, L.M., (2000) Proteins, 40, p. 378
  • Houzelstein, D., Gonçalves, I.R., Fadden, A.J., Sidhu, S.S., Cooper, D.N.W., Drickamer, K., Leffler, H., Poirier, F., Mol. Biol. E, 2004 (21), p. 1177
  • Seetharaman, J., Kanigsberg, A., Slaaby, R., Leffler, H., Barondes, S.H., Rini, J.M., (1998) J. Biol. Chem, 273, p. 13047
  • Brewer, C.F., (2005) Glycoconj. J, 19, p. 459
  • Boraston, A.B., Ficko-Blean, E., Healey, M., (2007) Biochemistry, 46, p. 11352
  • Thobhani, S., Ember, B., Siriwardena, A., Boons, G., (2003) J. Am. Chem. Soc, 125, p. 7154
  • Case, D. A.; Darden, T. A.; Cheatham, T. E. III; Simmerling, C. L.; Wang, J.; Duke, R. E.; Luo, R.; Merz, K. M.; Pearlman, D. A.; Crowley, M.; Walker, R. C.; Zhang, W.; Wang, B.; Hayik, S.; Roitberg, A.; Seabra, G.; Wong, K. F.; Paesani, F.; Wu, X.; Brozell, S.; Gohlke, H.; Yang, L.; Tan, C.; Hornak, V.; Cui, G.; Mathews, D. H.; Steinbrecher, T.; Seetin, M. G.; Sagui, C.; Babin, V.; Ross, C. W.; Kollman, P. A. AMBER 10 University of California: San Francisco, CA, 2006; Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz, K.M., Ferguson, D.M., Spellmeyer, D.C., Kollman, P.A., (1995) J. Am. Chem. Soc, 117, p. 5179
  • Case, D.A., Cheatham, T.E., Darden, T.A., Gohlke, H., Luo, R., Merz, K.M.J., Onufriev, A., Woods, R.J., (2005) J. Comput. Chem, 26, p. 1668
  • Berendsen, H.J.C., Postma, J.P.M., Van Gunsteren, W.F., DiNola, A., Haak, J.R., (1984) J. Chem. Phys, 81, p. 3684
  • Humphrey, W., Dalke, A., Schulten, K., (1996) J. Mol. Graphics, 14, p. 33

Citas:

---------- APA ----------
Gauto, D.F., Di Lella, S., Guardia, C.M.A., Estrin, D.A. & Martí, M.A. (2009) . Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy. Journal of Physical Chemistry B, 113(25), 8717-8724.
http://dx.doi.org/10.1021/jp901196n
---------- CHICAGO ----------
Gauto, D.F., Di Lella, S., Guardia, C.M.A., Estrin, D.A., Martí, M.A. "Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy" . Journal of Physical Chemistry B 113, no. 25 (2009) : 8717-8724.
http://dx.doi.org/10.1021/jp901196n
---------- MLA ----------
Gauto, D.F., Di Lella, S., Guardia, C.M.A., Estrin, D.A., Martí, M.A. "Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy" . Journal of Physical Chemistry B, vol. 113, no. 25, 2009, pp. 8717-8724.
http://dx.doi.org/10.1021/jp901196n
---------- VANCOUVER ----------
Gauto, D.F., Di Lella, S., Guardia, C.M.A., Estrin, D.A., Martí, M.A. Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy. J Phys Chem B. 2009;113(25):8717-8724.
http://dx.doi.org/10.1021/jp901196n