Abstract
The three-dimensional structures of the adenylation domains (A) of eight modules of SyrE, a peptide synthetase involved in the biosynthesis of syringomycin, was investigated by homology modeling using as a template the adenylation domain of gramicidin synthetase 1. Multiple sequence alignment of the adenylation domains of each of the eight modules of SyrE, allowed to identify the residues which delimitate the active site pockets. The active sites of the A domains of SyrE1 and SyrE2, involved in the insertion of the two serine residues in syringomycin, are essentially equivalent. The docking of these models with L-Ser and D-Ser showed that L-Ser is preferred as a substrate on the basis of stabilizing interactions. This is in accordance with previously shown stereo-specificity of these modules. Analogous investigation carried out on the modules SyrE3 and SyrE4 showed the preference for the L-isomer of their substrate, 2,4-diaminobutyric acid. In addition, the model of SyrE8, whose substrate amino acid is arginine, allowed to evidence specificity — conferring residues for this residue, which had not been previously reported
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References
Conti, E., Stachelhaus, T., Marahiel, M.A., and Brick, P., 1997, Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S. EMBO J. 16: 4174–4183.
Döhren, von H., Keller, V., Vater, J., and Zocher, R., 1997, Multifunctional peptide synthetases. Chem. Rev. 97: 2675–2705.
Fukuchi, N., Isogai, A., Nakayama, J., Takayama, S., Yamashita, S., Suyama, K., Takemoto, J.Y. and Suzuki, A., 1992, Structure and stereochemistry of three phytotoxins, syringomycin, syringotoxin and syringostatin, produced by Pseudomonas syringae pv. syringae. J. Chem. Soc. Perkin Trans. 1: 1149–1157.
Grgurina, I., and Benincasa, M., 1994, Evidence of the non ribosomal biosynthetic mechanism in the formation of syringomycin and syringopeptin, bioactive lipodepsipeptides of the phytopathogenic bacterium Pseudomonas syringae pv. syringae. It. Biochem. Soc. Trans. 5: 143.
Guenzi, E., Galli, G., Grgurina, I., Gross, D.C., and Grandi, G., 1998, Characterisation of the syringomycin synthetase gene cluster. J. Biol. Chem. 273: 32857–32863.
Kabsch, W., and Sander, C., 1983, Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22: 2577–2637.
Laskowski, R.A., MacArthur, M.W., Moss, D.S., and Thornton, J.M., 1993, PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Cryst. 26: 283–291.
Scaloni, A., Bachmann, R.C., Takemoto, J.Y., Barra, D., Simmaco, M., and Ballio, A., 1994, Stereochemical structure of syringomycin, a phytotoxic metabolite of Pseudomonas syringae pv. syringae. Nat. Prod. Letters 4: 159–164.
Segre, A., Bachman, R.C., Ballio, A., Bossa, F., Grgurina, I., Iacobellis, N.S., Marino, G., Pucci, P., Simmaco, M., and Takemoto, J.Y., 1989, The structure of syringomycin A1, E and G. FEBS Lett. 255: 27–31.
Stachelhaus, T., Mootz, H.D., and Marahiel, M.A., 1999, The specificity-conferring code of adenylation domains in non ribosomal peptide synthetase. Chem. Biol. 6: 493–505.
Sali, A., Potterton, L., Yuan, F., Van Vlijmen, H., and Karplus, M., 1995, Evaluation of comparative protein modeling by MODELLER. Proteins 23: 318–326.
Sippl, M.J., 1993, Recognition of errors in three-dimensional structures of proteins. Proteins 17: 355–362.
Thompson, J.D., Higgins, D.G., and Gibson, T.J., 1994, CLUSTALW: improving the sensitivity of progressive multiple alignment through sequence weighting, positionspecific gap penalties and weight matrix choice. Nucleic Acids Res. 22: 4673–4680.
Zhang, J.H., Quigley, N.B., and Gross, D.C., 1995, Analysis of the syrB and syrC gene of Pseudomonas syringae pv. syringae indicates that syringomycin is synthesised by a thiotemplate mechanism. J. Bacteriol. 177: 4009–4020.
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Pascarella, S., Giovannini, P., Grgurina, I. (2003). Substrate Specificity of Syringomycin Synthetase Adenylation Domains. In: Iacobellis, N.S., et al. Pseudomonas syringae and related pathogens. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-0133-4_23
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DOI: https://doi.org/10.1007/978-94-017-0133-4_23
Publisher Name: Springer, Dordrecht
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