Artículo

Este artículo es de Acceso Abierto y puede ser descargado en su versión final desde nuestro repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

A highly sulfated 3-linked β-arabinan (Ab1) with arabinose in the pyranose form was obtained from green seaweed Codium vermilara (Bryopsidales). It comprised major amounts of units sulfated on C-2 and C-4 and constitutes the first polysaccharide of this type isolated in the pure form and fully characterized. Ab1 showed anticoagulant activity by global coagulation tests. Less sulfated arabinans obtained from the same seaweed have less or no activity. Ab1 exerts its activity through direct and indirect (antithrombin- and heparin cofactor II-mediated) inhibition of thrombin. Direct thrombin inhibition was studied in detail. By native PAGE, it was possible to detect formation of a complex between Ab1 and human thrombin (HT). Ab1 binding to HT was measured by fluorescence spectroscopy. CD spectra of the Ab1 complex suggested that ligand binding induced a small conformational change on HT. Ab1-thrombin interactions were studied by molecular dynamic simulations using the persulfated octasaccharide as model compound. Most carbohydrate-protein contacts would occur by interaction of sulfate groups with basic amino acid residues on the surface of the enzyme, more than 60% of them being performed by the exosite 2-composing residues. In these interactions, the sulfate groups on C-2 were shown to interact more intensely with the thrombin structure. In contrast, the disulfated oligosaccharide does not promote major conformational modifications at the catalytic site when complexed to exosite 1. These results show that this novel pyranosic sulfated arabinan Ab1 exerts its anticoagulant activity by a mechanism different from those found previously for other sulfated polysaccharides and glycosaminoglycans. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Registro:

Documento: Artículo
Título:Anticoagulant activity of a unique sulfated pyranosic (1→3)-β-L- arabinan through direct interaction with thrombin
Autor:Fernández, P.V.; Quintana, I.; Cerezo, A.S.; Caramelo, J.J.; Pol-Fachin, L.; Verli, H.; Estevez, J.M.; Ciancia, M.
Filiación:Cátedra de Química de Biomoléculas, Departamento de Biología Aplicada y Alimentos, Universidad de Buenos Aires, Av. San Martín 4453, 1417 Buenos Aires, Argentina
Laboratorio de Hemostasia y Trombosis, Departamento de Química Biológica, Universidad de Buenos Aires, Pabellón 2, C1428EHA Buenos Aires, Argentina
Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR), Departamento de Química Orgánica, Universidad de Buenos Aires, Pabellón 2, C1428EHA Buenos Aires, Argentina
Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), CONICET, Av. Patricias Argentinas 435, 1405 Buenos Aires, Argentina
Programa de Pos-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, 90610-000 Porto Alegre, Rio Grande do Sul, Brazil
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, C1428EHA Buenos Aires, Argentina
Palabras clave:Amino acid residues; Anticoagulant activities; Antithrombin; Arabinans; Catalytic sites; CD spectra; Conformational change; Direct interactions; Glycosaminoglycans; Green seaweed; Heparin cofactor; Ligand binding; Model compound; Octasaccharide; Pyranose; Sulfate groups; Sulfated polysaccharides; Thrombin inhibition; Amino acids; Coagulation; Computer simulation; Fluorescence spectroscopy; Oligosaccharides; Polysaccharides; Seaweed; Enzymes; algal extract; amino acid; arabinose; carbohydrate; heparin cofactor II; oligosaccharide; polysaccharide; protein; sulfated pyranosic beta arabinan; thrombin; unclassified drug; anticoagulation; article; blood clotting test; catalysis; circular dichroism; conformational transition; drug mechanism; drug structure; fluorescence spectroscopy; ligand binding; molecular dynamics; nonhuman; priority journal; protein modification; protein protein interaction; seaweed; simulation; Animals; Anticoagulants; Biophysics; Blood Coagulation; Carbohydrate Conformation; Cattle; Cell Wall; Circular Dichroism; Electrophoresis; Gas Chromatography-Mass Spectrometry; Humans; Kinetics; Magnetic Resonance Spectroscopy; Methylation; Models, Chemical; Molecular Conformation; Polysaccharides; Protein Binding; Pyrans; Seaweed; Spectroscopy, Fourier Transform Infrared; Thrombin; Caulerpales; Codium vermilara
Año:2013
Volumen:288
Número:1
Página de inicio:223
Página de fin:233
DOI: http://dx.doi.org/10.1074/jbc.M112.386441
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:amino acid, 65072-01-7; arabinose, 147-81-9; heparin cofactor II, 81604-65-1; protein, 67254-75-5; thrombin, 869858-13-9, 9002-04-4; Anticoagulants; Polysaccharides; Pyrans; Thrombin, 3.4.21.5; araban, 11078-27-6; arabinan sulfate, 145378-97-8
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00219258_v288_n1_p223_Fernandez.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v288_n1_p223_Fernandez

Referencias:

  • Love, J., Percival, E., The polysaccharides of the green seaweed Codium fragile. Part II. The water-soluble sulphated polysaccharides (1964) J. Chem. Soc., pp. 3338-3345
  • Ciancia, M., Quintana, I., Vizcarguenaga, M.I., Kasulin, L., De Dios, A., Estevez, J.M., Cerezo, A.S., Polysaccharides from the green seaweeds Codium fragile and C. vermilara with controversial effects on hemostasis (2007) International Journal of Biological Macromolecules, 41 (5), pp. 641-649. , DOI 10.1016/j.ijbiomac.2007.08.007, PII S0141813007002097
  • Estevez, J.M., Fernández, P.V., Kasulin, L., Dupree, P., Ciancia, M., Chemical and in situ characterization of macromolecular components of the cell walls from the green seaweed Codium fragile (2009) Glycobiology, 19, pp. 212-228
  • Bilan, M.I., Vinogradova, E.V., Shashkov, A.S., Usov, A.I., Structure of a highly pyruvylated galactan sulfate from the Pacific green alga Codium yezoense (Bryopsidales, Chlorophyta) (2007) Carbohydrate Research, 342 (3-4), pp. 586-596. , DOI 10.1016/j.carres.2006.11.008, PII S0008621506005210
  • Farias, E.H.C., Pomin, V.H., Valente, A.-P., Nader, H.B., Rocha, H.A.O., Mourao, P.A.S., A preponderantly 4-sulfated, 3-linked galactan from the green alga Codium isthmocladum (2008) Glycobiology, 18 (3), pp. 250-259. , DOI 10.1093/glycob/cwm139
  • Ohta, Y., Lee, J.-B., Hayashi, K., Hayashi, T., Isolation of sulfated galactan from Codium fragile and its antiviral effect (2009) Biol. Pharm. Bull., 32, pp. 892-898
  • Hayakawa, Y., Hayashi, T., Lee, J., Srisomporn, P., Maeda, M., Ozawa, T., Sakuragawa, N., Inhibition of thrombin by sulfated polysaccharides isolated from green seaweeds (2000) Biochim. Biophys. Acta, 1543, pp. 86-94
  • Siddhanta, A.K., Shanmugam, M., Mody, K.H., Goswami, A.M., Ramavat, B.K., Sulphated polysaccharides of Codium dwarkense Boergs. from the west coast of India: Chemical composition and blood anticoagulant activity (1999) International Journal of Biological Macromolecules, 26 (2-3), pp. 151-154. , DOI 10.1016/S0141-8130(99)00079-3, PII S0141813099000793
  • Ciancia, M., Quintana, I., Cerezo, A.S., Overview of anticoagulant activity of sulfated polysaccharides from seaweeds in relation to their structures, focusing on those of green seaweeds (2010) Curr. Med. Chem., 17, pp. 2503-2529
  • Jurd, K.M., Rogers, D.J., Blunden, G., McLellan, D.S., Anticoagulant properties of sulphated polysaccharides and a proteoglycan from Codium fragile ssp. atlanticum (1995) J. Appl. Phycol., 7, pp. 339-345
  • Matsubara, K., Matsuura, Y., Hori, K., Miyazawa, K., An anticoagulant proteoglycan from the marine green alga, Codium pugniformis (2000) Journal of Applied Phycology, 12 (1), pp. 9-14. , DOI 10.1023/A:1008174115350
  • Boraso De Zaixso, A.L., Marine Chlorophyta of Argentina (2004) Hist. Nat., 3, pp. 95-119
  • Knutsen, S.H., Grasdalen, H., Characterization of water extractable polysaccharides from Norwegian Furcellaria umbricalis (Huds) Lamour (Gigartinales, Rhodophyceae) by IR and NMR spectroscopy (1987) Botanica Marina, 30, pp. 497-505
  • Dubois, M., Gilles, K.A., Hamilton, J.K., Rebers, P.A., Smith, F., Colorimetric method of determination of sugars and related substances (1956) Anal. Chem., 28, pp. 350-356
  • Dodgson, K.S., Price, R.G., A note on the determination of the ester sulphate content of sulphated polysaccharides (1962) Biochem. J., 84, pp. 106-110
  • Lowry, O.H., Rosenbrough, N.J., Farr, A.L., Protein measurements with the Folin phenol reagent (1951) J. Biol. Chem., 193, pp. 265-275
  • Stevenson, T.T., Furneaux, R.H., Chemical methods for the analysis of sulphated galactans from red algae (1991) Carbohydr. Res., 210, pp. 277-298
  • Park, J.T., Johnson, M.J., Asub microdetermination of glucose (1949) J. Biol. Chem., 181, pp. 149-151
  • Navarro, D.A., Flores, M.L., Stortz, C.A., Microwave-assisted desulfation of sulfated polysaccharides (2007) Carbohydrate Polymers, 69 (4), pp. 742-747. , DOI 10.1016/j.carbpol.2007.02.009, PII S0144861707001221
  • Ciucanu, I., Kerek, K., A simple and rapid method for the permethylation of carbohydrates (1984) Carbohydr. Res., 134, pp. 209-217
  • Laffan, M.A., Bradshaw, A.E., Investigation of haemostasis (1995) Practical Haematology, pp. 297-315. , Dacie, J. V., and Lewis, S. M., eds . Churchill Livingstone, New York
  • Colliec, S., Fischer, A.M., Tapon-Bretaudiere, J., Boisson, C., Durand, P., Jozefonvicz, J., Anticoagulant properties of a fucoidan fraction (1991) Thromb. Res., 64, pp. 143-154
  • Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S.R., Hofsteenge, J., The refined 1.9 Å crystal structure of human α-thrombin: Interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment (1989) EMBO Journal, 8 (11), pp. 3467-3475
  • Van De Locht, A., Lamba, D., Bauer, M., Huber, R., Friedrich, T., Kröger, B., Höffken, W., Bode, W., Two heads are better than one. Crystal structure of the insect-derived double domain Kazal inhibitor rhodniin in complex with thrombin (1995) EMBO J., 14, pp. 5149-5157
  • Fernandes, C.L., Sachett, L.G., Pol-Fachin, L., Verli, H., GROMOS96 43a1 performance in predicting oligosaccharide conformational ensembles within glycoproteins (2010) Carbohydr. Res., 345, pp. 663-671
  • Pol-Fachin, L., Serrato, R.V., Verli, H., Solution conformation and dynamics of exopolysaccharides from Burkholderia species (2010) Carbohydr. Res., 345, pp. 1922-1931
  • Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J., AutoDock4 and AutoDockTools4. Automated docking with selective receptor flexibility (2009) J. Comput. Chem., 30, pp. 2785-2791
  • Hess, B., Bekker, H., Berendsen, H.J.C., Fraaije, J.G.E.M., LINCS: A Linear Constraint Solver for molecular simulations (1997) Journal of Computational Chemistry, 18 (12), pp. 1463-1472
  • Darden, T., York, D., Pedersen, L., Particle mesh Ewald. An N-log(N) method for Ewald sums in large systems (1993) J. Chem. Phys., 98, pp. 10089-10092
  • Berendsen, H.J., Postma, J.P., Van Gunsteren, W.F., DiNola, A., Haak, J.R., Molecular dynamics with a coupling to an external bath (1984) J. Chem. Phys., 81, pp. 3684-3690
  • Bussi, G., Donadio, D., Parrinello, M., Canonical sampling through velocity rescaling (2007) J. Chem. Phys., 126, p. 014101
  • Hess, B., Kutzner, C., Van Der Spoel, D., Lindahl, E., GROMACS 4. Algorithms for highly efficient, load-balanced, and scalable molecular simulation (2008) J. Chem. Theory Comput., 4, pp. 435-447
  • Scott, W.R.P., Hunenberger, P.H., Tironi, I.G., Mark, A.E., Billeter, S.R., Fennen, J., Torda, A.E., Van Gunsteren, W.F., The GROMOS biomolecular simulation program package (1999) Journal of Physical Chemistry A, 103 (19), pp. 3596-3607
  • Spedding, H., Infrared Spectroscopy (1962) Methods in Carbohydrate Chemistry, 1, pp. 539-550. , Analysis and Preparation of Sugars Whistler, R. L., and Wolfrom, M. L., eds Academic Press, Inc., New York
  • Prado-Fernandez, J., Rodriguez-Vazquez, J.A., Tojo, E., Andrade, J.M., Quantitation of κ-, ι- and κ-carrageenans by mid-infrared spectroscopy and PLS regression (2003) Analytica Chimica Acta, 480 (1), pp. 23-37. , DOI 10.1016/S0003-2670(02)01592-1
  • Stortz, C.A., Cerezo, A.S., The 13C NMR spectroscopy of carrageenans. Calculation of chemical shifts and computer-aided structural determination (1992) Int. J. Biol. Macromol., 14, pp. 237-242
  • Noseda, M.D., Cerezo, A.S., Room temperature, low-field 13C-n.m.r. spectra of degraded carrageenans. Part III. Autohydrolysis of a λ carrageenan and of its alkali-treated derivative (1993) Int. J. Biol. Macromol., 15, pp. 177-181
  • Cinelli, L.P., Andrade, L., Valente, A.P., Mourão, P.A., Sulfated α-L-galactans from the sea urchin ovary. Selective 6-desulfation as eggs are spawned (2010) Glycobiology, 20, pp. 702-709
  • Pereira, M.S., Vilela-Silva, A.-C.E.S., Valente, A.-P., Mourao, P.A.S., A 2-sulfated, 3-linked α-L-galactan is an anticoagulant polysaccharide (2002) Carbohydrate Research, 337 (21-23), pp. 2231-2238. , DOI 10.1016/S0008-6215(02)00215-X, PII S000862150200215X
  • Becker, C.F., Guimarães, J.A., Mourão, P.A., Verli, H., Conformation of sulfated galactan and sulfated fucan in aqueous solutions. Implications to their anticoagulant activities (2007) J. Mol. Graph. Model., 26, pp. 391-399
  • Bock, K., Pedersen, C., Carbon-13 nuclear magnetic resonance spectroscopy of monosaccharides (1983) Adv. Carbohydr. Chem. Biochem., 41, pp. 27-66
  • Zhuo, K., Liu, H., Zhang, X., Liu, Y., Wang, J., A 13CNMR study on the interactions of calcium chloride/potassium chloride with pyranosides in D2O (2008) Carbohydr. Res., 343, pp. 2428-2432
  • Odonmazig, P., Ebringerova, A., Machova, E., Alfoldi, J., Structural and molecular properties of the arabinogalactan isolated from Mongolian larchwood (Larix dahurica L.) (1994) Carbohydrate Research, 252, pp. 317-324. , DOI 10.1016/0008-6215(94)84145-4
  • Ishii, T., Konishi, T., Ito, Y., Ono, H., Ohnishi-Kameyama, M., Maeda, I., A β-(1 → 3)-arabinopyranosyltransferase that transfers a single arabinopyranose onto arabino-oligosaccharides in mung bean (Vigna radiate) hypocotyls (2005) Phytochemistry, 66 (20), pp. 2418-2425. , DOI 10.1016/j.phytochem.2005.08.007, PII S0031942205003614
  • Shashkov, A.S., Lipkind, G.M., Knirel, Y.A., Kochetkov, N.K., Stereochemical factors determining the effects of glycosylation on the13C chemical shifts in carbohydrates (1988) Magn. Res. Chem., 26, pp. 735-747
  • Carroll, W.E., Thromboplastins, heparin, and Polybrene (1999) Am. J. Clin. Pathol., 111, p. 565
  • Li, W., Johnson, D.J.D., Esmon, C.T., Huntington, J.A., Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin (2004) Nature Structural and Molecular Biology, 11 (9), pp. 857-862. , DOI 10.1038/nsmb811
  • Salvagnini, C., Michaux, C., Remiche, J., Wouters, J., Charlier, P., Marchand-Brynaert, J., Design, synthesis and evaluation of graftable thrombin inhibitors for the preparation of blood-compatible polymer materials (2005) Organic and Biomolecular Chemistry, 3 (23), pp. 4209-4220. , DOI 10.1039/b510239a
  • Fredenburgh, J.C., Stafford, A.R., Weitz, J.I., Evidence for allosteric linkage between exosites 1 and 2 of thrombin (1997) Journal of Biological Chemistry, 272 (41), pp. 25493-25499. , DOI 10.1074/jbc.272.41.25493
  • Sheehan, J.P., Sadler, J.E., Molecular mapping of the heparin-binding exosite of thrombin (1994) Proceedings of the National Academy of Sciences of the United States of America, 91 (12), pp. 5518-5522. , DOI 10.1073/pnas.91.12.5518
  • Matsubara, K., Matsuura, Y., Bacic, A., Liao, M.-L., Hori, K., Miyazawa, K., Anticoagulant properties of a sulfated galactan preparation from a marine green alga, Codium cylindricum (2001) International Journal of Biological Macromolecules, 28 (5), pp. 395-399. , DOI 10.1016/S0141-8130(01)00137-4, PII S0141813001001374
  • Fernández, P.V., Estevez, J.M., Cerezo, A.S., Ciancia, M., Sulfated β-D-mannan from the green seaweed Codium vermilara (2012) Carbohydr. Polym., 87, pp. 916-919
  • Sommer-Knudsen, J., Bacic, A., Clarke, A.E., Hydroxyproline-rich plant glycoproteins (1998) Phytochemistry, 47 (4), pp. 483-497. , DOI 10.1016/S0031-9422(97)00724-3, PII S0031942297007243
  • Somerville, C., Bauer, S., Brininstool, G., Facette, M., Hamann, T., Milne, J., Osborne, E., Youngs, H., Toward a systems approach to understanding plant cell walls (2004) Science, 306 (5705), pp. 2206-2211. , DOI 10.1126/science.1102765
  • Clarke, A.E., Anderson, R.L., Stone, B.A., Form and function of arabinogalactans and arabinogalactan-proteins (1979) Phytochemistry, 18, pp. 521-540
  • Tryfona, T., Liang, H.-C., Kotake, T., Kaneko, S., Marsh, J., Ichinose, H., Lovegrove, A., Dupree, P., Carbohydrate structural analysis of wheat flour arabinogalactan protein (2010) Carbohydr. Res., 345, pp. 2648-2656
  • Uehara, T., Takeshita, M., Maeda, M., Studies on anticoagulant-active arabinan sulfates from the green alga, Codium latum (1992) Carbohydr. Res., 23, pp. 309-311
  • Nilsson, S., Piculell, L., Helix-coil transitions of ionic polysaccharides analyzed within the Poisson-Boltzmann cell model. 4. Effects of site-specific counterion binding (1991) Macromolecules, 24 (13), pp. 3804-3811
  • Robinson, G., Morris, E.R., Rees, D.A., Role of double helices in carrageenan gelation. The domain model (1980) J. Chem. Soc. Chem. Commun., pp. 152-153
  • Aspinall, G.O., Isolation and fractionation of Polysaccharides (1982) The Polysaccharides, 1, pp. 19-34. , Aspinall, G. O., ed Academic Press, Inc., Orlando, FL
  • Kelton, J.G., Warkentin, T.E., Heparin-induced thrombocytopenia. A historical perspective (2008) Blood, 112, pp. 2607-2616
  • Kam, P.C.A., Kaur, N., Thong, C.L., Direct thrombin inhibitors: Pharmacology and clinical relevance (2005) Anaesthesia, 60 (6), pp. 565-574. , DOI 10.1111/j.1365-2044.2005.04192.x
  • Di, N.M., Middeldorp, S., Buller, H.R., Direct thrombin inhibitors (2005) New England Journal of Medicine, 353 (10), pp. 1028-1040. , http://content.nejm.org/cgi/reprint/353/10/1028.pdf, DOI 10.1056/NEJMra044440
  • Melo, F.R., Pereira, M.S., Foguel, D., Mourao, P.A.S., Antithrombin-mediated anticoagulant activity of sulfated polysaccharides: Different mechanisms for heparin and sulfated galactans (2004) Journal of Biological Chemistry, 279 (20), pp. 20824-20835. , DOI 10.1074/jbc.M308688200
  • Mao, W., Zang, X., Li, Y., Zhang, H., Sulfated polysaccharides from marine green algae Ulva conglobata and their anticoagulant activity (2006) Journal of Applied Phycology, 18 (1), pp. 9-14. , DOI 10.1007/s10811-005-9008-4

Citas:

---------- APA ----------
Fernández, P.V., Quintana, I., Cerezo, A.S., Caramelo, J.J., Pol-Fachin, L., Verli, H., Estevez, J.M.,..., Ciancia, M. (2013) . Anticoagulant activity of a unique sulfated pyranosic (1→3)-β-L- arabinan through direct interaction with thrombin. Journal of Biological Chemistry, 288(1), 223-233.
http://dx.doi.org/10.1074/jbc.M112.386441
---------- CHICAGO ----------
Fernández, P.V., Quintana, I., Cerezo, A.S., Caramelo, J.J., Pol-Fachin, L., Verli, H., et al. "Anticoagulant activity of a unique sulfated pyranosic (1→3)-β-L- arabinan through direct interaction with thrombin" . Journal of Biological Chemistry 288, no. 1 (2013) : 223-233.
http://dx.doi.org/10.1074/jbc.M112.386441
---------- MLA ----------
Fernández, P.V., Quintana, I., Cerezo, A.S., Caramelo, J.J., Pol-Fachin, L., Verli, H., et al. "Anticoagulant activity of a unique sulfated pyranosic (1→3)-β-L- arabinan through direct interaction with thrombin" . Journal of Biological Chemistry, vol. 288, no. 1, 2013, pp. 223-233.
http://dx.doi.org/10.1074/jbc.M112.386441
---------- VANCOUVER ----------
Fernández, P.V., Quintana, I., Cerezo, A.S., Caramelo, J.J., Pol-Fachin, L., Verli, H., et al. Anticoagulant activity of a unique sulfated pyranosic (1→3)-β-L- arabinan through direct interaction with thrombin. J. Biol. Chem. 2013;288(1):223-233.
http://dx.doi.org/10.1074/jbc.M112.386441