gtp phosphohydrolase linked elongation factors


Summary: Factors that utilize energy from the hydrolysis of GTP to GDP for peptide chain elongation. EC 3.6.1.-.

Top Publications

  1. Knudsen C, Kjaersgård I, Wiborg O, Clark B. Mutation of the conserved Gly94 and Gly126 in elongation factor Tu from Escherichia coli. Elucidation of their structural and functional roles. Eur J Biochem. 1995;228:176-83 pubmed
    ..The mutants only exhibit minor changes compared to the wild type with respect to in vitro translation of a poly(U) messenger. ..
  2. Abrahams J, Acampo J, Kraal B, Bosch L. The influence of tRNA located at the P-site on the turnover of EF-Tu.GTP on ribosomes. Biochimie. 1991;73:1089-92 pubmed
    ..GTP than ribosomes with an empty P-site. The data suggest that this is mainly caused by an increased affinity of EF-Tu.GTP for ribosomes with a filled P-site rather than by an enhanced reactivity of the GTPase centre. ..
  3. Marzouki A, Sontag B, Lavergne J, Vidonne C, Reboud J, Reboud A. Effect of ADP-ribosylation and phosphorylation on the interaction of elongation factor 2 with guanylic nucleotides. Biochimie. 1991;73:1151-6 pubmed
  4. Hilgenfeld R. Regulatory GTPases. Curr Opin Struct Biol. 1995;5:810-7 pubmed
    ..In the field of elongation factors (EFs), three very important structures have been determined: EF-G, the ternary complex of EF-Tu.GTP with aminoacyl-tRNA, and the EF-Tu.EF-Ts complex...
  5. Kohno K, Uchida T, Ohkubo H, Nakanishi S, Nakanishi T, Fukui T, et al. Amino acid sequence of mammalian elongation factor 2 deduced from the cDNA sequence: homology with GTP-binding proteins. Proc Natl Acad Sci U S A. 1986;83:4978-82 pubmed
  6. Jurnak F. The ABC of EF-G. Structure. 1994;2:785-8 pubmed
  7. Liljas A. Imprinting through molecular mimicry. Protein synthesis. Curr Biol. 1996;6:247-9 pubmed
    ..Part of the structure of translational elongation factor G, in a complex with GDP, resembles the tRNA bound in a ternary complex with elongation factor Tu and GTP; this 'molecular mimicry' extends to charge distribution as well as shape. ..
  8. Tezuka M, CHLADEK S. The elongation factor Tu.GTPase reaction: effect of 2'(3')-O-aminoacyl oligoribonucleotides. Biochim Biophys Acta. 1988;950:463-5 pubmed
    ..GTPase, it follows that EF-Tu probably directly recognizes structure of nucleobases in the aa-tRNA 3'-terminus, with the 3'-terminal adenine playing the most important role. ..
  9. Harmark K, Anborgh P, Merola M, Clark B, Parmeggiani A. Substitution of aspartic acid-80, a residue involved in coordination of magnesium, weakens the GTP binding and strongly enhances the GTPase of the G domain of elongation factor Tu. Biochemistry. 1992;31:7367-72 pubmed
    ..This enhanced catalytic activity represents the most striking consequence of the mutation and stresses the key role of Asp80 in the GTPase of EF-Tu.(ABSTRACT TRUNCATED AT 250 WORDS) ..

More Information


  1. Al Karadaghi S, Aevarsson A, Garber M, Zheltonosova J, Liljas A. The structure of elongation factor G in complex with GDP: conformational flexibility and nucleotide exchange. Structure. 1996;4:555-65 pubmed
    ..The conformation of EF-G-GDP around the nucleotide-binding site may be related to the mechanism of nucleotide exchange...
  2. Mistou M, Cool R, Parmeggiani A. Effects of ions on the intrinsic activities of c-H-ras protein p21. A comparison with elongation factor Tu. Eur J Biochem. 1992;204:179-85 pubmed
    ..5-10, suggesting that the bell-shaped behaviour of this activity in the absence of the antibiotic is due to denaturation. This implies similar properties in the catalytic mechanism of these two guanine-nucleotide-binding proteins. ..
  3. Abel K, Yoder M, Hilgenfeld R, Jurnak F. An alpha to beta conformational switch in EF-Tu. Structure. 1996;4:1153-9 pubmed
    ..The alpha to beta switch in EF-Tu may represent a prototypical activation mechanism for other protein families. ..
  4. Boriack Sjodin P, Margarit S, Bar Sagi D, Kuriyan J. The structural basis of the activation of Ras by Sos. Nature. 1998;394:337-43 pubmed
    ..Sos does not impede the binding sites for the base and the ribose of GTP or GDP, so the Ras-Sos complex adopts a structure that allows nucleotide release and rebinding. ..
  5. Miyazaki M, Uritani M, Kagiyama H. The yeast peptide elongation factor 3 (EF-3) carries an active site for ATP hydrolysis which can interact with various nucleoside triphosphates in the absence of ribosomes. J Biochem. 1988;104:445-50 pubmed
    ..From experiments on protection against tryptic digestion, we determined that intricate conformational changes of the factor molecule occur upon interaction with the substrate XTP and ribosomes. ..
  6. Caldas T, El Yaagoubi A, Kohiyama M, Richarme G. Purification of elongation factors EF-Tu and EF-G from Escherichia coli by covalent chromatography on thiol-sepharose. Protein Expr Purif. 1998;14:65-70 pubmed
    ..The specific reactivities of the elongation factors with thiol-Sepharose allow their efficient purification and suggest that they possess hitherto undiscovered properties connected with their reactive thiols. ..
  7. Lill R, Robertson J, Wintermeyer W. Binding of the 3' terminus of tRNA to 23S rRNA in the ribosomal exit site actively promotes translocation. EMBO J. 1989;8:3933-8 pubmed
    ..The co-operative interaction between the E site and the EF-G binding site, which are distantly located on the 50S ribosomal subunit, is probably mediated by a conformational change of 23S rRNA. ..
  8. Caldas T, El Yaagoubi A, Richarme G. Chaperone properties of bacterial elongation factor EF-Tu. J Biol Chem. 1998;273:11478-82 pubmed
    ..These results suggest that EF-Tu, in addition to its function in translation elongation, might be implicated in protein folding and protection from stress. ..
  9. Zeidler W, Egle C, Ribeiro S, Wagner A, Katunin V, Kreutzer R, et al. Site-directed mutagenesis of Thermus thermophilus elongation factor Tu. Replacement of His85, Asp81 and Arg300. Eur J Biochem. 1995;229:596-604 pubmed
    ..thermophilus EF-Tu. Mutation of His85, a residue which is not directly involved in the nucleotide binding, thus influences the interaction of EF-Tu domains, nucleotide binding and the efficiency and rate of GTPase activity. ..
  10. Weijland A, Parlato G, Parmeggiani A. Elongation factor Tu D138N, a mutant with modified substrate specificity, as a tool to study energy consumption in protein biosynthesis. Biochemistry. 1994;33:10711-7 pubmed
    ..With rate-limiting amounts of XTP the K'm of its XTPase activity corresponded to the K'm for XTP of poly(phenylalanine) synthesis (0.3-0.6 microM).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  11. Martemyanov K, Yarunin A, Liljas A, Gudkov A. An intact conformation at the tip of elongation factor G domain IV is functionally important. FEBS Lett. 1998;434:205-8 pubmed
    ..It is concluded that the native conformation of the loop is important for the factor-promoted translocation in the ribosome. The functional importance of the entire EF-G domain IV is discussed...
  12. Kubarenko A, Sergiev P, Rodnina M. [GTPases of translational apparatus]. Mol Biol (Mosk). 2005;39:746-61 pubmed
    ..This review is devoted to the functional peculiarities of translational GTPases as related to other G-proteins. Particularly, to the putative GTPase activation mechanism, structure and functional cycles. ..
  13. Rodnina M, Serebryanik A, Ovcharenko G, El skaya A. ATPase strongly bound to higher eukaryotic ribosomes. Eur J Biochem. 1994;225:305-10 pubmed
    ..Rabbit liver ribosomes seem to stimulate the ATPase activity of yeast EF-3 similar to the mechanism in yeast ribosomes, though less efficiently. ..
  14. Dunkle J, Cate J. Ribosome structure and dynamics during translocation and termination. Annu Rev Biophys. 2010;39:227-44 pubmed publisher
    ..Finally, we review recent advances in understanding how bacteria handle errors in both translocation and termination. ..
  15. Abrahams J, van Raaij M, Ott G, Kraal B, Bosch L. Kirromycin drastically reduces the affinity of Escherichia coli elongation factor Tu for aminoacyl-tRNA. Biochemistry. 1991;30:6705-10 pubmed
    ..Modification with N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) decreases the affinity of EF-Tu-kirromycin-GTP for aminoacyl-tRNA, just like it does in the absence of the antibiotic. ..
  16. Rodnina M, Savelsbergh A, Matassova N, Katunin V, Semenkov Y, Wintermeyer W. Thiostrepton inhibits the turnover but not the GTPase of elongation factor G on the ribosome. Proc Natl Acad Sci U S A. 1999;96:9586-90 pubmed
    ..The results indicate that thiostrepton inhibits a structural transition of the 1067 region of 23S rRNA that is important for functions of EF-G after GTP hydrolysis. ..
  17. Vorstenbosch E, Pape T, Rodnina M, Kraal B, Wintermeyer W. The G222D mutation in elongation factor Tu inhibits the codon-induced conformational changes leading to GTPase activation on the ribosome. EMBO J. 1996;15:6766-74 pubmed
    ..Increasing the Mg2+ concentration appears to overcome the inhibition by screening the negative charges. ..
  18. Martemyanov K, Liljas A, Gudkov A. Increased functional activity of elongation factor G with G16V mutation in the GTP-binding domain. Biochemistry (Mosc). 1998;63:1216-9 pubmed
    ..coli. The mutated protein with an uncleavable GTP analog also has an increased affinity to the ribosomes. ..
  19. Bilgin N, Claesens F, Pahverk H, Ehrenberg M. Kinetic properties of Escherichia coli ribosomes with altered forms of S12. J Mol Biol. 1992;224:1011-27 pubmed
    ..We use our in vitro findings to discuss the in vivo physiology of these mutants as well as mechanistic features of E. coli translation. ..
  20. Krab I, Parmeggiani A. Functional-structural analysis of threonine 25, a residue coordinating the nucleotide-bound magnesium in elongation factor Tu. J Biol Chem. 1999;274:11132-8 pubmed
    ..They emphasize the importance of the Thr-25-Mg2+ bond, although its absence is compatible with protein synthesis and thus with an active overall conformation of EF-Tu. ..
  21. Zeef L, Mesters J, Kraal B, Bosch L. A growth-defective kirromycin-resistant EF-Tu Escherichia coli mutant and a spontaneously evolved suppression of the defect. Gene. 1995;165:39-43 pubmed
    ..We also show that strains containing the segregated tufA Q124K mutation formed filaments. ..
  22. Masullo M, De Vendittis E, Bocchini V. Archaebacterial elongation factor 1 alpha carries the catalytic site for GTP hydrolysis. J Biol Chem. 1994;269:20376-9 pubmed
    ..A molecular mechanism for this activation is proposed. ..
  23. March P. Membrane-associated GTPases in bacteria. Mol Microbiol. 1992;6:1253-7 pubmed
    ..In spite of similarities to well-studied eukaryotic proteins the signalling pathways of these cellular regulators, with the exception of NodQ, have not yet been elucidated. ..
  24. Ahmadian M, Kreutzer R, Blechschmidt B, Sprinzl M. Site-directed mutagenesis of Thermus thermophilus EF-Tu: the substitution of threonine-62 by serine or alanine. FEBS Lett. 1995;377:253-7 pubmed
    ..GTP. These observations are in agreement with the tertiary structure of EF-Tu.GTP, in which threonine-62 is interacting with the Mg2+ ion, gamma-phosphate of GTP and a water molecule, which is presumably involved in the GTP hydrolysis. ..
  25. Swart G, Parmeggiani A. tRNA and the guanosinetriphosphatase activity of elongation factor Tu. Biochemistry. 1989;28:327-32 pubmed
    ..When EF-Tu acts as a component of the ternary complex formed with GTP and aa-tRNA, the presence of tRNA in the P-site strongly increases the GTPase activity.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  26. Hou Y, Yaskowiak E, March P. Carboxyl-terminal amino acid residues in elongation factor G essential for ribosome association and translocation. J Bacteriol. 1994;176:7038-44 pubmed
    ..We propose that all of these mutations are present in a domain that is essential for ribosome association and that GTP hydrolysis was deficient as a secondary consequence of impaired binding to 70S ribosomes. ..
  27. Laalami S, Grentzmann G, Bremaud L, Cenatiempo Y. Messenger RNA translation in prokaryotes: GTPase centers associated with translational factors. Biochimie. 1996;78:577-89 pubmed
    ..Of the prokaryotic translational factors, IF2, EF-Tu, SELB, EF-G and RF3 are GTP-binding proteins. In this review we summarize the latest findings on the structures and the roles of these GTPases in the translational process. ..
  28. Jacquet E, Parmeggiani A. Substitution of Val20 by Gly in elongation factor Tu. Effects on the interaction with elongation factors Ts, aminoacyl-tRNA and ribosomes. Eur J Biochem. 1989;185:341-6 pubmed
    ..mRNA, as a consequence of a longer pausing of EF-TuG20 on the ribosome. In conclusion, position 20 in EF-Tu is important for coordinating the allosteric mechanisms controlling the action of EF-Tu and its ligands. ..
  29. Mesters J, Martien de Graaf J, Kraal B. Divergent effects of fluoroaluminates on the peptide chain elongation factors EF-Tu and EF-G as members of the GTPase superfamily. FEBS Lett. 1993;321:149-52 pubmed
    ..Interestingly, in the absence of ribosomes both EF-Tu an EF-G remain totally unaffected by fluoraluminates. For members of the GTPase superfamily such differential effects have not been described before. ..
  30. Keeling P, Fast N, McFadden G. Evolutionary relationship between translation initiation factor eIF-2gamma and selenocysteine-specific elongation factor SELB: change of function in translation factors. J Mol Evol. 1998;47:649-55 pubmed
    ..The overall topology of the GTPase tree further suggests that the eIF-2gamma/SELB group may represent an ancient subfamily of GTPases that diverged prior to the last common ancestor of extant life. ..
  31. Pedersen G, Rattenborg T, Knudsen C, Clark B. The role of Glu259 in Escherichia coli elongation factor Tu in ternary complex formation. Protein Eng. 1998;11:101-8 pubmed
  32. Cetin R, Anborgh P, Cool R, Parmeggiani A. Functional role of the noncatalytic domains of elongation factor Tu in the interactions with ligands. Biochemistry. 1998;37:486-95 pubmed
  33. Nagel K, Voigt J. An inhibitor of elongation factor G (EF-G) GTPase present in the ribosome wash of Escherichia coli: a complex of initiation factors IF1 and IF3?. Biochim Biophys Acta. 1992;1129:145-8 pubmed
    ..Therefore, IF1 as well as the EF-G GTPase inhibitor do not influence the ribosome-dependent EF-G GTPase by affecting the association of ribosomal subunits. ..
  34. Grentzmann G, Kelly P, Laalami S, Shuda M, Firpo M, Cenatiempo Y, et al. Release factor RF-3 GTPase activity acts in disassembly of the ribosome termination complex. RNA. 1998;4:973-83 pubmed
    ..Based on our results, we propose a model of how RF3 might function in translational termination and ribosome recycling. ..
  35. Burdett V. Tet(M)-promoted release of tetracycline from ribosomes is GTP dependent. J Bacteriol. 1996;178:3246-51 pubmed
    ..Furthermore, while Tet(M) protects translation from tetracycline inhibition in a defined system, it is unable to substitute for either EF-G or elongation factor Tu. ..
  36. Kinzy T, Merrick W. Characterization of a limited trypsin digestion form of eukaryotic elongation factor 1 alpha. J Biol Chem. 1991;266:4099-105 pubmed
    ..Limited trypsin digestion of modified protein indicates that none of these reagents cross-links GTP to the first 69 amino acids of EF-1 alpha, which includes the first GTP binding consensus element, GXXXXGK. ..
  37. Chinali G, Vanlinden F, Cocito C. Action of virginiamycin M on the stability of different ribosomal complexes to ultracentrifugation. Biochim Biophys Acta. 1988;950:67-74 pubmed
    ..This interpretation is supported by the finding that the ribosome-promoted protection of aminoacyl-tRNA against spontaneous hydrolysis is suppressed by virginiamycin M. ..
  38. Ganoza M, Cunningham C, Green R. A new factor from Escherichia coli affects translocation of mRNA. J Biol Chem. 1995;270:26377-81 pubmed
    ..We propose that W functions by ejecting tRNAs from ribosomes in a step that precedes the movement of mRNA during translocation. ..
  39. Andersen C, Wiborg O. Escherichia coli elongation-factor-Tu mutants with decreased affinity for aminoacyl-tRNA. Eur J Biochem. 1994;220:739-44 pubmed
    ..The Kd is about 20-times higher for H66A compared to wild type. Our results strongly suggest that His66 and His118 play major roles in stabilization of the ternary complex. ..
  40. Pape T, Wintermeyer W, Rodnina M. Induced fit in initial selection and proofreading of aminoacyl-tRNA on the ribosome. EMBO J. 1999;18:3800-7 pubmed
    ..As kinetically favored incorporation of the correct substrate has also been suggested for DNA and RNA polymerases, the present findings indicate that induced fit may contribute to the fidelity of template-programed systems in general. ..
  41. Nissen P, Thirup S, Kjeldgaard M, Nyborg J. The crystal structure of Cys-tRNACys-EF-Tu-GDPNP reveals general and specific features in the ternary complex and in tRNA. Structure. 1999;7:143-56 pubmed
    ..The structure of the 'kissing complex' shows a quasicontinuous helix with a distinct shape determined by the number of base pairs...
  42. Rodnina M, Savelsbergh A, Katunin V, Wintermeyer W. Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome. Nature. 1997;385:37-41 pubmed
    ..By coupling the free energy of GTP hydrolysis to translocation, EF-G serves as a motor protein to drive the directional movement of transfer and messenger RNAs on the ribosome. ..
  43. Jensen M, Cool R, Mortensen K, Clark B, Parmeggiani A. Structure-function relationships of elongation factor Tu. Isolation and activity of the guanine-nucleotide-binding domain. Eur J Biochem. 1989;182:247-55 pubmed
    ..The inability of the G domain to sustain poly(Phe) synthesis is in agreement with the apparent lack of formation of a ternary complex between the G domain.GTP complex and aa-tRNA.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  44. Raimo G, Masullo M, Scarano G, Bocchini V. The site for GTP hydrolysis on the archaeal elongation factor 2 is unmasked by aliphatic alcohols. Biochimie. 1996;78:832-7 pubmed
    ..The stimulatory effect of ethylene glycol/Ba2+ was attributed to the increased affinity for GTP, probably related to a conformational change occurring in a hydrophobic region near the catalytic site. ..
  45. Thompson J, Musters W, Cundliffe E, Dahlberg A. Replacement of the L11 binding region within E.coli 23S ribosomal RNA with its homologue from yeast: in vivo and in vitro analysis of hybrid ribosomes altered in the GTPase centre. EMBO J. 1993;12:1499-504 pubmed
    ..coli and yeast rRNAs allows the hybrid ribosomes to function competently in protein synthesis and also preserves the interaction with thiostrepton. ..
  46. Ogasawara T, Ito K, Igarashi K, Yutsudo T, Nakabayashi N, Takeda Y. Inhibition of protein synthesis by a Vero toxin (VT2 or Shiga-like toxin II) produced by Escherichia coli O157:H7 at the level of elongation factor 1-dependent aminoacyl-tRNA binding to ribosomes. Microb Pathog. 1988;4:127-35 pubmed
    ..VT2 did not affect Met-tRNAf binding to ribosomes, non-enzymatic binding of aminoacyl-tRNA to ribosomes, peptide bond formation or translocation. ..
  47. Miyazaki M, Kagiyama H. Soluble factor requirements for the Tetrahymena peptide elongation system and the ribosomal ATPase as a counterpart of yeast elongation factor 3 (EF-3). J Biochem. 1990;108:1001-8 pubmed
    ..It was also shown that the ribosomal nucleotidase plays a pivotal role in the elongation cycle in other eukaryotes. ..
  48. Laurberg M, Mansilla F, Clark B, Knudsen C. Investigation of functional aspects of the N-terminal region of elongation factor Tu from Escherichia coli using a protein engineering approach. J Biol Chem. 1998;273:4387-91 pubmed
  49. Weijland A, Parmeggiani A. Toward a model for the interaction between elongation factor Tu and the ribosome. Science. 1993;259:1311-4 pubmed
    ..This stoichiometry of two is associated with the binding of the correct aa-tRNA to the ribosome. ..
  50. Hall C, Watkins J, Georgopapadakou N. Effects of elfamycins on elongation factor Tu from Escherichia coli and Staphylococcus aureus. Antimicrob Agents Chemother. 1989;33:322-5 pubmed
    ..13 microM. This suggests that the observed high MICs of kirromycin and its congeners in S. aureus reflect a kirromycin-resistant EF-Tu rather than permeability constraints. ..
  51. Kahns S, Lund A, Kristensen P, Knudsen C, Clark B, Cavallius J, et al. The elongation factor 1 A-2 isoform from rabbit: cloning of the cDNA and characterization of the protein. Nucleic Acids Res. 1998;26:1884-90 pubmed
    ..In contrast, the GDP dissociation rate constant is approximately 7 times higher for eEF1A-1 than for eEF1A-2. The nucleotide preference ratio (GDP/GTP) for eEF1A-1 was 0.82, while the preference ratio for eEF1A-2 was 1.50. ..
  52. Masullo M, Ianniciello G, Arcari P, Bocchini V. Properties of truncated forms of the elongation factor 1alpha from the archaeon Sulfolobus solfataricus. Eur J Biochem. 1997;243:468-73 pubmed
  53. Rattenborg T, Nautrup Pedersen G, Clark B, Knudsen C. Contribution of Arg288 of Escherichia coli elongation factor Tu to translational functionality. Eur J Biochem. 1997;249:408-14 pubmed
    ..However, the mutants' abilities to bind aminoacyl-tRNA and protect the labile aminoacyl bond were impaired, especially where the charge had been reversed. ..