Artículos de revistas
The Structure Of The D49 Phospholipase A2 Piratoxin Iii From Bothrops Pirajai Reveals Unprecedented Structural Displacement Of The Calcium-binding Loop: Possible Relationship To Cooperative Substrate Binding
Registro en:
Acta Crystallographica - Section D Biological Crystallography. , v. 59, n. 2, p. 255 - 262, 2003.
9074449
10.1107/S0907444902021467
2-s2.0-0037319939
Autor
Rigden D.J.
Hwa L.W.
Marangoni S.
Toyama M.H.
Polikarpov I.
Institución
Resumen
Snake venoms are rich sources of phospholipase A2 homologues, both active calcium-binding Asp49 enzymes and essentially inactive Lys49 proteins. They are responsible for multiple pharmacological effects, some of which are dependent on catalytic activity and others of which are not. Here, the 2.4 Å X-ray crystal structure of an active Asp49 phospholipase A2 from the venom of the snake Bothrops pirajai, refined to conventional and free R values of 20.1 and 25.5%, respectively, is reported. Unusually for phospholipases A2, the dependence of the enzyme rate on the substrate concentration is sigmoidal, implying cooperativity of substrate binding. The unprecedented structural distortion seen for the calcium-binding loop in the present structure may therefore be indicative of a T-state enzyme. An explanation of the interaction between the substrate-binding sites based on the canonical phospholipase A2 dimer is difficult. However, an alternative putative dimer interface identified in the crystal lattice brings together the calcium-binding loops of neighbouring molecules, along with the C-terminal regions which are disulfide bonded to those loops, thereby offering a possible route of communication between active sies. 59 2 255 262 Adams, P.D., Pannu, N.S., Read, R.J., Brünger, A.T., (1997) Proc. Natl Acad. Sci. USA, 94, pp. 5018-5023 Arni, R.K., Fontes, M.R., Barberato, C., Gutierrez, J.M., Diaz, C., Ward, R.J., (1999) Arch. Biochem. Biophys., 366, pp. 177-182 Barton, G.J., (1993) Protein Eng., 6, pp. 37-40 Beghini, D.G., Toyama, M.H., Hyslop, S., Sodek, L.C., Novello, J.C., Marangoni, S., (2000) J. Protein Chem., 19, pp. 679-684 Brünger, A.T., (1992) Nature (London), 355, pp. 472-474 Brünger, A.T., Adams, P.D., Clore, G.M., DeLano, W.L., Gros, P., Grosse-Kunstleve, R.W., Jiang, J.S., Warren, G.L., (1998) Acta Cryst., D54, pp. 905-921 Burke, J.R., Witmer, M.R., Tredup, J., Micanovic, R., Gregor, K.R., Lahiri, J., Tramposch, K.M., Villafranca, J.J., (1995) Biochemistry, 34, pp. 15165-15174 Carredano, E., Westerlund, B., Persson, B., Saarinen, M., Ramaswamy, S., Eaker, D., Eklund, H., (1998) Toxicon, 36, pp. 75-92 Cha, S.S., Lee, D., Adams, J., Kurdyla, J.T., Jones, C.S., Marshall, L.A., Bolognese, B., Oh, B.H., (1996) J. Med. Chem., 39, pp. 3878-3881 Cho, W., Kézdy, F.J., (1991) Methods Enzymol., 197, pp. 75-79 (1994) Acta Cryst., D50, pp. 760-763 Cowtan, K.D., Zhang, K.Y., (1999) Prog. Biophys. Mol. Biol., 72, pp. 245-270 Dessen, A., Tang, J., Schmidt, H., Stahl, M., Clark, J.D., Seehra, J., Somers, W.S., (1999) Cell, 97, pp. 349-360 Devedjiev, Y., Popov, A., Atanasov, B., Bartunik, H.D., (1997) J. Mol. Biol., 266, pp. 160-172 Dijkstra, B.W., Drenth, J., Kalk, K., Vandermaalen, P.J., (1978) J. Mol. Biol., 124, pp. 53-60 Esnouf, R.M., (1997) J. Mol. Graph., 15, pp. 132-134 Felsenstein, J., (1989) Cladistics, 5, pp. 164-166 Fremont, D.H., Anderson, D.H., Wilson, I.A., Dennis, E.A., Xuong, N.H., (1993) Proc. Natl Acad. Sci. USA, 90, pp. 342-346 Frishman, D., Argos, P., (1995) Proteins, 23, pp. 566-579 Gerrard, J.M., Robinson, P., Narvey, M., McNicol, A., (1993) Biochem. Cell Biol., 71, pp. 432-439 Gutierrez, J.M., Lomonte, B., (1995) Toxicon, 33, pp. 1405-1424 Holland, D.R., Clancy, L.L., Muchmore, S.W., Ryde, T.J., Einspahr, H.M., Finzel, B.C., Heinrikson, R.L., Watenpaugh, K.D., (1990) J. Biol. Chem., 265, pp. 17649-17656 Holm, L., Sander, C., (1998) Nucleic Acids Res., 26, pp. 316-319 Holzer, M., Mackessy, S.P., (1996) Toxicon, 34, pp. 1149-1155 Jones, T.A., Zou, J.Y., Cowan, S.W., Kjeldgaard, M., (1991) Acta Cryst., A47, pp. 110-119 Keith, C., Feldman, D.S., Deganello, S., Glick, J., Ward, K.B., Jones, E.O., Sigler, P.B., (1981) J. Biol. Chem., 256, pp. 8602-8607 Kleywegt, G.J., (1999) Acta Cryst., D55, pp. 1878-1884 Kleywegt, G.J., Brünger, A.T., (1996) Structure, 4, pp. 897-904 Kleywegt, G.J., Jones, T.A., (1996) Acta Cryst., D52, pp. 829-832 Kleywegt, G.J., Jones, T.A., (1998) Acta Cryst., D54, pp. 1119-1131 Kraulis, P.J., (1991) J. Appl. Cryst., 24, pp. 946-950 Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M., (1993) J. Appl. Cryst., 26, pp. 283-291 Lawrence, M.C., Colman, P.M., (1993) J. Mol. Biol., 234, pp. 946-950 Leahy, D.J., Axel, R., Hendrickson, W.A., (1992) Cell, 68, pp. 1145-1162 Lee, W.H., Da Silva Giotto, M.T., Marangoni, S., Toyama, M.H., Polikarpov, I., Garratt, R.C., (2001) Biochemistry, 40, pp. 28-36 Lloret, S., Moreno, J.J., (1993) Toxicon, 31, pp. 949-956 Lu, G., (2000) J. Appl. Cryst., 33, pp. 176-183 Mancuso, L.C., Correa, M.M., Vieira, C.A., Cunha, O.A., Lachat, J.J., De Araújo, H.S., Ownby, C.L., Giglio, J.R., (1995) Toxicon, 33, pp. 615-626 Maraganore, J.M., Merutka, G., Cho, W., Welches, W., Kezdy, F.J., Heinrikson, R.L., (1984) J. Biol. Chem., 259, pp. 13839-13843 Matthews, B.W., (1968) J. Mol. Biol., 33, pp. 491-497 Nayal, M., Di Cera, E., (1996) J. Mol. Biol., 256, pp. 228-234 Otwinowski, Z., (1993) Proceedings of the CCP4 Study Weekend. Data Collection and Processing, pp. 56-62. , Warrington: Daresbury Laboratory Pan, H., Liu, X.L., Ou-Yang, L.L., Yang, G.Z., Zhou, Y.C., Li, Z.P., Wu, X.F., (1998) Toxicon, 36, pp. 1155-1163 Pannu, N.S., Read, R.J., (1996) Acta Cryst., A52, pp. 659-668 Perbandt, M., Wilson, J.C., Eschenburg, S., Mancheva, I., Aleksiev, B., Genov, N., Willingmann, P., Betzel, C., (1997) FEBS Lett, 412, pp. 573-577 Polikarpov, I., Perles, L.A., De Oliveira, R.T., Oliva, G., Castellano, E.E., Garratt, R., Craievich, A., (1998) J. Synchrotron Rad., 5, pp. 72-76 Polikarpov, I., Teplyakov, A., Oliva, G., (1997) Acta Cryst., D53, pp. 734-737 Read, R.J., (1986) Acta Cryst., A42, pp. 140-149 Renetseder, R., Brunie, S., Dijkstra, B.W., Drenth, J., Sigler, P.B., (1985) J. Biol. Chem., 260, pp. 11627-11634 Rice, L.M., Brünger, A.T., (1994) Proteins, 19, pp. 277-290 Rychlewski, L., Jaroszewski, L., Li, W., Godzik, A., (2000) Protein Sci., 9, pp. 232-241 Sali, A., Blundell, T.L., (1993) J. Mol. Biol., 234, pp. 779-815 Schevitz, R.W., (1995) Nature Struct. Biol., 2, pp. 458-465 Scott, D.L., Otwinowski, Z., Gelb, M.H., Sigler, P.B., (1990) Science, 250, pp. 1563-1566 Scott, D.L., Sigler, P.B., (1994) Adv. Protein Chem., 45, pp. 53-88 Shimohigashi, Y., Tani, A., Matsumoto, H., Nakashima, K., Yamaguchi, Y., (1995) J. Biochem., 118, pp. 1037-1044 Da Silva Giotto, M.T., Garratt, R.C., Oliva, G., Mascarenhas, Y.P., Giglio, J.R., Cintra, A.C., De Azevedo W.F., Jr., Ward, R.J., (1998) Proteins, 30, pp. 442-454 Soares, A.M., Andriao-Escarso, S.H., Bortoleto, R.K., Rodrigues-Simioni, L., Arni, R.K., Ward, R.J., Gutierrez, J.M., Giglio, J.R., (2001) Arch. Biochem. Biophys., 387, pp. 188-196 Toyama, M.H., Costa, P.D., Novello, J.C., De Oliveira, B., Giglio, J.R., Da Cruz-Hofling, M.A., Marangoni, S., (1999) J. Protein Chem., 18, pp. 371-378 Toyama, M.H., Soares, A.M., Wen-Hwa, L., Polikarpov, I., Giglio, J.R., Marangoni, S., (2000) Biochimie, 82, pp. 245-250 Tsai, I.H., Wang, Y.M., Au, L.C., Ko, T.P., Chen, Y.H., Chu, Y.F., (2000) Eur. J. Biochem., 267, pp. 6684-6691 Vagin, A., Teplyakov, A., (1997) J. Appl. Cryst., 30, pp. 1022-1025 Valdar, W.S., Thornton, J.M., (2001) J. Mol. Biol., 313, pp. 399-416 Verity, M.A., (1992) Neurotoxicology, 13, pp. 139-147 Ward, R.J., Alves, A.R., Ruggiero Neto, J., Arni, R.K., Casari, G.A., (1998) Protein Eng., 11, pp. 285-294