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Mechanism and evolution of multidomain aminoacyl-tRNA synthetases revealed by their inhibition by analogues of a reaction intermediate, and by properties of truncated forms

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DOI: 10.4236/jbise.2013.610115    3,465 Downloads   4,928 Views   Citations

ABSTRACT

Many enzymes which catalyze the conversion of large substrates are made of several structural domains belonging to the same polypeptide chain. Transfer RNA (tRNA), one of the substrates of the multidomain aminoacyl-tRNA synthetases (aaRS), is an L-shaped molecule whose size in one dimension is similar to that of its cognate aaRS. Crystallographic structures of aaRS/tRNA complexes show that these enzymes use several of their structural domains to interact with their cognate tRNA. This mini review discusses first some aspects of the evolution and of the flexibility of the pentadomain bacterial glutamyl-tRNA synthetase (GluRS) revealed by kinetic and interaction studies of complementary truncated forms, and then illustrates how stable analogues of aminoacyl-AMP intermediates have been used to probe conformational changes in the active sites of Escherichia coli GluRS and of the nondiscriminating aspartyl-tRNA synthetase (ND-AspRS) of Pseudomonas aeruginosa.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Lapointe, J. (2013) Mechanism and evolution of multidomain aminoacyl-tRNA synthetases revealed by their inhibition by analogues of a reaction intermediate, and by properties of truncated forms. Journal of Biomedical Science and Engineering, 6, 943-946. doi: 10.4236/jbise.2013.610115.

References

[1] Branden, C. and Tooze, J. (1999) Introduction to protein structure. 2nd Edition, Garland Publishing, Inc., New York.
[2] Ataide, S.F. and Ibba, M. (2006) Small molecules: Big players in the evolution of protein synthesis. ACS Chemical Biology, 1, 285-297. http://dx.doi.org/10.1021/cb600200k
[3] Giege, R., Touze, E., Lorber, B., Theobald-Dietrich, A. and Sauter, C. (2008) Crystallogenesis trends of free and liganded aminoacyl-tRNA synthetases. Crystal Growth & Design, 8, 4297-4306. http://dx.doi.org/10.1021/cg8007766
[4] First, E.A. (2005) Catalysis of the tRNA aminoacylation reaction. In: Ibba, M., Francklynand C. and Cusack, S., Eds., The Aminoacyl-tRNASynthetases, Landes Bioscience, Georgetown, pp. 328-352.
[5] Lapointe, J. and Giegé, R. (1991). Transfer RNAs and aminoacyl-tRNA synthetases in eukaryotes. In: H. Trachsel, Ed., Translation in Eukaryotes, CRC Press, pp 35-69.
[6] Schimmel, P., Giege, R., Moras, D. and Yokoyama, S. (1993) An operational RNA code for amino acids and possible relationship to genetic code. Proceedings of the National Academy of Sciences of the United States of America, 90, 8763-8768. http://dx.doi.org/10.1073/pnas.90.19.8763
[7] Chuang, G.-Y., Mehra-Chaudhary, R., Ngan, C.-H., Zerbe, B.S., Kozakov, D., Vajda, S. and Beamer, L.J. (2010) Domain motion and interdomain hot spotsin a multidomain enzyme. Protein Science, 19, 1662-1672. http://dx.doi.org/10.1002/pro.446
[8] Sekine, S.-I., Nureki, O., Dubois, D.Y., Bernier, S., Chênevert, R., Lapointe, J., Vassylyev, D.G. and Yokoyama, S. (2003) ATP binding by glutamyl-tRNA synthetase is switched to the productive mode by tRNA binding. EMBO Journal, 22, 676-688. http://dx.doi.org/10.1093/emboj/cdg053
[9] Dubois, D.Y., Blais, S.P., Huot, J.L. and Lapointe, J. (2009) A C-truncated glutamyl-tRNAsynthetase specific for tRNAGlu is stimulated by its free complementary distal domain: Mechanistic and evolutionary implications. Biochemistry, 48, 6012-6021. http://dx.doi.org/10.1021/bi801690f
[10] Dasgupta, S., Saha, R., Dey, C., Banerjee, R., Roy, S. and Basu, G. (2009) The role of the catalytic domain of E. coli GluRS in tRNAGln discrimination. FEBS Letters, 583, 2114-2120.
http://dx.doi.org/10.1016/j.febslet.2009.05.041
[11] Ebel, J.P., Bonnet, J., Kern, D., Befort, N., Bollack, C., Fasiolo, F., Gangloff, J. and Dirheimer, G. (1973) Factors determining the specificity of the tRNA aminoacylation reaction; non absolute specificity of tRNA-aminoacyl-tRNA recognition and particular importance of the maximal velocity. Biochimie, 55, 547-557. http://dx.doi.org/10.1016/S0300-9084(73)80415-8
[12] Giegé, R. and Springer, M. (2012) Aminoacyl-tRNA synthetases in the bacterial world. In: Curtiss, R., III, Kaper, J.B., Squires, C.L., Karp, P.D., Neidhardt, F.C. and Slauch, J.M. Eds., EcoSal, ASM Press, Washington DC.
[13] Latterich, M. and Corbeil, J. (2008) Label-free detection of biomolecular interactions in real time with a nano-porous silicon-based detection method. Proteome Science, 6, 31.
http://dx.doi.org/10.1186/1477-5956-6-31
[14] Madore, E., Florentz, C., Giegé, R., Sekine, S.-I., Yokoyama, S. and Lapointe, J. (1999) Effect of modified nucleotides on Escherichia coli tRNAGlu structure and on its aminoacylation by glutamyl-tRNA synthetase; predominant and distinct roles of the mnm5 and s2 modifications of U34. European Journal of Biochemistry, 266, 1128-1135. http://dx.doi.org/10.1046/j.1432-1327.1999.00965.x
[15] Weygand-Durasevic, I., Rogers, M.J. and Soll, D. (1994) Connecting anticodon recognition with the active site of Escherichia coli glutaminyl-tRNA synthetase. Journal of Molecular Biology, 240, 111-118. http://dx.doi.org/10.1006/jmbi.1994.1425
[16] Chênevert, R., Bernier, S. and Lapointe, J. (2003) Inhibitors of aminoacyl-tRNA synthetases as antibiotics and tools for structural and mechanistic studies. In: J. Lapointe and L. Brakier-Gingras, Eds., Translation Mechanisms, Landes Bioscience/Eureka.com and Kluwer Academic/Plenum Publishers, pp. 416-428
[17] Vondenhoff, G.H.M. and Van Aerschot, A. (2011) Aminoacyl-tRNA synthetase inhibitors as potential antibiotics. European Journal of Medicinal Chemistry, 46, 5227-5236.
http://dx.doi.org/10.1016/j.ejmech.2011.08.049
[18] Bernier, S., Dubois, D.Y., Habegger-Polomat, C., Gagnon, L.-P., Lapointe, J. and Chênevert, R. (2005) Glutamylsulfamoyladenosine and Pyroglutamylsulfamoyladenosine are competitive inhibitors of E. coli glutamyl-tRNA synthetase. Journal of Enzyme Inhibition and Medicinal Chemistry, 20, 61-67. http://dx.doi.org/10.1080/14756360400002007
[19] Bernard, D., Akochy, P.-M., Bernier, S., Fisette, O., Coté Brousseau, O., Chênevert, R., Roy, P.H. and Lapointe. J. (2007) Inhibition by L-aspartol adenylate of a nondiscriminating aspartyl-tRNA synthetase reveals differences between the interactions of its active site with tRNAAsp and tRNAAsn. Journal of Enzyme Inhibition and Medicinal Chemistry, 22, 77-82.
http://dx.doi.org/10.1080/14756360600952316
[20] Akochy, P.-M., Bernard, D., Roy, P.H. and Lapointe, J. (2004) Direct glutaminyl-tRNA biosynthesis and indirect asparaginyl-tRNA biosynthesis in Pseudomonas aeruginosa PAO1. Journal of Bacteriology, 186, 767-776. http://dx.doi.org/10.1128/JB.186.3.767-776.2004
[21] Huot, J.L., Lapointe, J., Chênevert, R., Bailly, M. and Kern, D. (2010) Glutaminyl-tRNA and asparaginyl-tRNA biosynthetic pathways and functions. In: Vederas, J.C., Ed., Comprehensive Natural Products Chemistry II, Vol. 5, Elsevier, Oxford, 383-431. http://dx.doi.org/10.1016/B978-008045382-8.00726-7
[22] Sauter, C., Lorber, B., Cavarelli, J., Moras, D. and Giegé, R. (2000) The free yeast aspartyl-tRNA synthetase differs from the tRNAAsp-complexed enzyme by structural changes in the catalytic site, hinge region, and anticodon-binding domain. Journal of Molecular Biology, 299, 1313-1324.
http://dx.doi.org/10.1006/jmbi.2000.3791

  
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