Lid L11 of the glutamine amidotransferase domain of CTP synthase mediates allosteric GTP activation of glutaminase activity

FEBS Journal

Volumn 272, Issue 3, 2005, Pages 856-864

  Willemoës, Martin ^a   Mølgaard, Anne ^a,b   Johansson, Eva ^a,c   Martinussen, Jan ^b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

^c EUROPEAN SYNCHROTRON RADIATION FACILITY   (France)

Author keywords

Allosteric regulation; Flexible loop; Lactococcus lactis; Nucleotide metabolism; Oxy anion hole

Indexed keywords

ARGININE; BACTERIAL ENZYME; CYTIDINE TRIPHOSPHATE; CYTIDINE TRIPHOSPHATE SYNTHASE; GLUTAMIC ACID; GLUTAMINASE; GLUTAMINE; GLUTAMINE AMIDOTRANSFERASE; GLYCINE; GUANOSINE TRIPHOSPHATE; MUTANT PROTEIN; TRANSFERASE; UNCLASSIFIED DRUG;

ALLOSTERISM; AMINO ACID SEQUENCE; ARTICLE; BINDING SITE; CHEMICAL REACTION; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME ASSAY; ENZYME KINETICS; ENZYME MECHANISM; ENZYME STRUCTURE; ENZYME SUBUNIT; ESCHERICHIA COLI; HYDROLYSIS; LACTOCOCCUS LACTIS; MOLECULAR INTERACTION; NONHUMAN; NUCLEOTIDE METABOLISM; PRIORITY JOURNAL; PROTEIN DOMAIN; SITE DIRECTED MUTAGENESIS; SYNTHESIS; THERMUS THERMOPHILUS; WILD TYPE;

ALLOSTERIC REGULATION; AMINO ACID SEQUENCE; BASE SEQUENCE; CARBON-NITROGEN LIGASES; DNA PRIMERS; ENZYME ACTIVATION; GLUTAMATE SYNTHASE; GLUTAMINASE; GUANOSINE TRIPHOSPHATE; KINETICS; MUTAGENESIS, SITE-DIRECTED; PROTEIN CONFORMATION; SUBSTRATE SPECIFICITY;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; LACTOCOCCUS LACTIS; OXY; THERMUS THERMOPHILUS;

EID: 13444283471     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2004.04525.x     Document Type: Article

References (34)

1. Zalkin H (1985) CTP synthetase. Methods Enzymol 113, 282-287.
2. Weng M, Makaroff CA & Zalkin H (1986) Nucleotide sequence of Escherichia coli pyrG encoding CTP synthetase. J Biol Chem 261, 5568-5574.
3. von der Saal W, Anderson PM & Villafranca JJ (1985) Mechanistic investigations of Escherichia coli cytidine-5′-triphosphate synthetase: detection of an intermediate by positional isotope exchange experiments. J Biol Chem 260, 14993-14997.
4. Lewis DA & Villafranca JJ (1989) Investigation of the mechanism of CTP synthetase using rapid quench and isotope partitioning methods. Biochemistry 28, 8454-8459.
5. Levitzki A & Koshland DE Jr (1972) Role of an allosteric effector: guanosine triphosphate activation in cytosine triphosphate synthetase. Biochemistry 11, 241-246.
6. Bearne SL, Hekmat O & Macdonnell JE (2001) Inhibition of Escherichia coli CTP synthase by glutamate gamma-semialdehyde and the role of the allosteric effector GTP in glutamine hydrolysis. Biochem J 356, 223-232.
7. Levitzki A, Stallcup WB & Koshland DE Jr (1971) Half-of-the-sites reactivity and the conformational states of cytidine triphosphate synthetase. Biochemistry 10, 3371-3378.
8. Kizaki H, Ohsaka F & Sakurada T (1982) Role of GTP in CTP synthetase from Ehrlich ascites tumor cells. Biochem Biophys Res Commun 108, 286-291.
9. Willemoes M (2004) Competition between ammonia derived from internal glutamine hydrolysis and hydroxylamine present in the solution for incorporation into UTP as catalysed by Lactococcus lactis CTP synthase. Arch Biochem Biophys 424, 105-111.
10. Willemoes M (2003) Thr-431 and Arg-433 are part of a conserved sequence motif of the glutamine amidotransferase domain of CTP synthases and are involved in GTP activation of the Lactococcus lactis enzyme. J Biol Chem 278, 9407-9411.
11. Simard D, Hewitt KA, Lunn F, Iyengar A & Bearne SL (2003) Limited proteolysis of Escherichia coli cytidine 5′-triphosphate synthase: identification of residues required for CTP formation and GTP-dependent activation of glutamine hydrolysis. Eur J Biochem 270, 2195-2206.
12. Willemoes M & Sigurskjold BW (2002) Steady-state kinetics of the glutaminase reaction of CTP synthase from Lactococcus lactis. Eur J Biochem 269, 4772-4779.
13. Endrizzi JA, Kim H, Anderson PM & Baldwin EP (2004) Crystal structure of Escherichia coli cytidine triphosphate synthetase, a nucleotide-regulated glutamine amidotransferase/ATP-dependent amidoligase fusion protein and homologue of anticancer and antiparasitic drug targets. Biochemistry 43, 6447-6463.
14. Lunn FA & Bearne SL (2004) Alternative substrates for wild-type and L109A E. coli CTP synthases. Eur J Biochem 271, 4204-4212.
15. Goto M, Omi R, Nakagawa N, Miyahara I & Hirotsu K (2004) Crystal structures of CTP synthetase reveal ATP, UTP, and glutamine binding sites. Structure (Camb) 12, 1413-1423.
16. Thoden JB, Huang X, Raushel FM & Holden HM (1999) The small subunit of carbamoyl phosphate synthetase: snapshots along the reaction pathway. Biochemistry 38, 16158-16166.
17. Mareya SM & Raushel FM (1994) A molecular wedge for triggering the amidotransferase activity of carbamoyl phosphate synthetase. Biochemistry 33, 2945-2950.
18. Miles BW, Banzon JA & Raushel FM (1998) Regulatory control of the amidotransferase domain of carbamoyl phosphate synthetase. Biochemistry 37, 16773-16779.
19. Myers RS, Jensen JR, Deras IL, Smith JL & Davisson VJ (2003) Substrate-induced changes in the ammonia channel for imidazole glycerol phosphate synthase. Biochemistry 42, 7013-7022.
20. Wellner VP & Meister A (1975) Enhancement of the glutaminase activity of carbamyl phosphate synthetase by alterations in the interaction between the heavy and light subunits. J Biol Chem 250, 3261-3266.
21. Thoden JB, Huang X, Kim J, Raushel FM & Holden HM (2004) Long-range allosteric transitions in carbamoyl phosphate synthetase. Protein Sci 13, 2398-2405.
22. Chittur SV, Klem TJ, Shafer CM & Davisson VJ (2001) Mechanism for acivicin inactivation of triad glutamine amidotransferases. Biochemistry 40, 876-887.
23. Weng ML & Zalkin H (1987) Structural role for a conserved region in the CTP synthetase glutamine amide transfer domain. J Bacteriol 169, 3023-3028.
24. Kim JH, Krahn JM, Tomchick DR, Smith JL & Zalkin H (1996) Structure and function of the glutamine phosphoribosylpyrophosphate amidotransferase glutamine site and communication with the phosphoribosylpyrophosphate site. J Biol Chem 271, 15549-15557.
25. Iyengar A & Bearne SL (2003) Aspartate-107 and leucine-109 facilitate efficient coupling of glutamine hydrolysis to CTP synthesis by Escherichia coli CTP synthase. Biochem J 369, 497-507.
26. Wadskov-Hansen SL, Willemoes M, Martinussen J, Hammer K, Neuhard J & Larsen S (2001) Cloning and verification of the Lactococcus lactis pyrG gene and characterization of the gene product, CTP synthase. J Biol Chem 276, 38002-38009.
27. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.
28. Long CW & Pardee AB (1967) Cytidine triphosphate synthetase of Escherichia coli B. I. Purification and kinetics. J Biol Chem 242, 4715-4721.
29. Willemoes M & Larsen S (2003) Substrate inhibition of Lactococcus lactis cytidine 5(′)-triphosphate synthase by ammonium chloride is enhanced by salt-dependent tetramer dissociation. Arch Biochem Biophys 413, 17-22.
30. Kraulis PJ (1991) MOLSCRIPT - a program to produce both detailed and schematic plots of protein structures. J Appl Crystallogr 24, 946-950.
31. Merrit EA (1994) Raster3D version 2.0. A program for photorealistic molecular graphics. Acta Crystallogr D Biol Crystallogr 50, 869-873.
32. Schneider TD & Stephens RM (1990) Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 18, 6097-6100.
33. Altschul SF, Gish W, Miller W, Myers EW & Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215, 403-410.
34. Shannon CE (1948) A mathematical theory of communication. Bell System Tech J 27, 379-423.