Decreased Sensitivity to Changes in the Concentration of Metal Ions as the Basis for the Hyperactivity of DtxR(E175K)

Journal of Molecular Biology

Volumn 390, Issue 1, 2009, Pages 112-123

  D'Aquino, J Alejandro ^a   Denninger, Andrew R ^a   Moulin, Aaron G ^a   D'Aquino, Katharine E ^b   Ringe, Dagmar ^a  

^a BRANDEIS UNIVERSITY   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

crystal structure; DtxR; iron dependent regulator; metal ion binding; protein stability

Indexed keywords

BACTERIAL DNA; CADMIUM; COBALT; DIPHTHERIA TOXIN REPRESSOR; IRON REGULATORY FACTOR; MANGANESE; METAL ION; NICKEL; UNCLASSIFIED DRUG; ZINC;

ARTICLE; BINDING AFFINITY; BINDING SITE; CALORIMETRY; CIRCULAR DICHROISM; CONCENTRATION PROCESS; CRYSTAL STRUCTURE; ELECTROPHORETIC MOBILITY; GENE MUTATION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY; SENSITIVITY ANALYSIS; THERMOSTABILITY; WILD TYPE;

CORYNEBACTERIUM DIPHTHERIAE; MUS; MYCOBACTERIUM TUBERCULOSIS;

EID: 67349281423     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2009.05.003     Document Type: Article

References (44)

1. Boyd J., Oza M.N., and Murphy J.R. Molecular cloning and DNA sequence analysis of a diphtheria tox iron-dependent regulatory element (dtxR) from Corynebacterium diphtheriae. Proc. Natl Acad. Sci. USA 87 (1990) 5968-5972
2. Schmitt M.P., Talley B.G., and Holmes R.K. Characterization of lipoprotein IRP1 from Corynebacterium diphtheriae, which is regulated by the diphtheria toxin repressor (DtxR) and iron. Infect. Immun. 65 (1997) 5364-5367
3. Schmitt M.P. Transcription of the Corynebacterium diphtheriae hmuO gene is regulated by iron and heme. Infect. Immun. 65 (1997) 4634-4641
4. Kunkle C.A., and Schmitt M.P. Analysis of the Corynebacterium diphtheriae DtxR regulon: identification of a putative siderophore synthesis and transport system that is similar to the Yersinia high-pathogenicity island-encoded yersiniabactin synthesis and uptake system. J. Bacteriol. 185 (2003) 6826-6840
5. Qian Y., Lee J.H., and Holmes R.K. Identification of a DtxR-regulated operon that is essential for siderophore-dependent iron uptake in Corynebacterium diphtheriae. J. Bacteriol. 184 (2002) 4846-4856
6. Lee J.H., Wang T., Ault K., Liu J., Schmitt M.P., and Holmes R.K. Identification and characterization of three new promoter/operators from Corynebacterium diphtheriae that are regulated by the diphtheria toxin repressor (DtxR) and iron. Infect. Immun. 65 (1997) 4273-4280
7. Tao X., and Murphy J.R. Binding of the metalloregulatory protein DtxR to the diphtheria tox operator requires a divalent heavy metal ion and protects the palindromic sequence from DNase I digestion. J. Biol. Chem. 267 (1992) 21761-21764
8. Spiering M.M., Ringe D., Murphy J.R., and Marletta M.A. Metal stoichiometry and functional studies of the diphtheria toxin repressor. Proc. Natl Acad. Sci. USA 100 (2003) 3808-3813
9. Schiering N., Tao X., Zeng H., Murphy J.R., Petsko G.A., and Ringe D. Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae. Proc. Natl Acad. Sci. USA 92 (1995) 9843-9850
10. Qiu X., Verlinde C.L., Zhang S., Schmitt M.P., Holmes R.K., and Hol W.G. Three-dimensional structure of the diphtheria toxin repressor in complex with divalent cation co-repressors. Structure 3 (1995) 87-100
11. D'Aquino J.A., Lattimer J.R., Denninger A., D'Aquino K.E., and Ringe D. Role of the N-terminal helix in the metal ion-induced activation of the diphtheria toxin repressor DtxR. Biochemistry 46 (2007) 11761-11770
12. Pohl E., Qui X., Must L.M., Holmes R.K., and Hol W.G. Comparison of high-resolution structures of the diphtheria toxin repressor in complex with cobalt and zinc at the cation-anion binding site. Protein Sci. 6 (1997) 1114-1118
13. Qiu X., Pohl E., Holmes R.K., and Hol W.G. High-resolution structure of the diphtheria toxin repressor complexed with cobalt and manganese reveals an SH3-like third domain and suggests a possible role of phosphate as co-corepressor. Biochemistry 35 (1996) 12292-12302
14. Pohl E., Holmes R.K., and Hol W.G. Crystal structure of a cobalt-activated diphtheria toxin repressor-DNA complex reveals a metal-binding SH3-like domain. J. Mol. Biol. 292 (1999) 653-667
15. White A., Ding X., vanderSpek J.C., Murphy J.R., and Ringe D. Structure of the metal-ion-activated diphtheria toxin repressor/tox operator complex. Nature 394 (1998) 502-506
16. Goranson-Siekierke J., Pohl E., Hol W.G., and Holmes R.K. Anion-coordinating residues at binding site 1 are essential for the biological activity of the diphtheria toxin repressor. Infect. Immun. 67 (1999) 1806-1811
17. Ding X., Zeng H., Schiering N., Ringe D., and Murphy J.R. Identification of the primary metal ion-activation sites of the diphtheria tox repressor by X-ray crystallography and site-directed mutational analysis. Nat. Struct. Biol. 3 (1996) 382-387
18. D'Aquino J.A., and Ringe D. Determinants of the Src homology domain 3-like fold. J. Bacteriol. 185 (2003) 4081-4086
19. Rangachari V., Marin V., Bienkiewicz E.A., Semavina M., Guerrero L., Love J.F., et al. Sequence of ligand binding and structure change in the diphtheria toxin repressor upon activation by divalent transition metals. Biochemistry 44 (2005) 5672-5682
20. Oram D.M., Must L.M., Spinler J.K., Twiddy E.M., and Holmes R.K. Analysis of truncated variants of the iron dependent transcriptional regulators from Corynebacterium diphtheriae and Mycobacterium tuberculosis. FEMS Microbiol. Lett. 243 (2005) 1-8
21. Sun L., vanderSpek J., and Murphy J.R. Isolation and characterization of iron-independent positive dominant mutants of the diphtheria toxin repressor DtxR. Proc. Natl Acad. Sci. USA 95 (1998) 14985-14990
22. Love J.F., vanderSpek J.C., and Murphy J.R. The src homology 3-like domain of the diphtheria toxin repressor (DtxR) modulates repressor activation through interaction with the ancillary metal ion-binding site. J. Bacteriol. 185 (2003) 2251-2258
23. Love J.F., vanderSpek J.C., Marin V., Guerrero L., Logan T.M., and Murphy J.R. Genetic and biophysical studies of diphtheria toxin repressor (DtxR) and the hyperactive mutant DtxR(E175K) support a multistep model of activation. Proc. Natl Acad. Sci. USA 101 (2004) 2506-2511
24. Glasfeld A., Guedon E., Helmann J.D., and Brennan R.G. Structure of the manganese-bound manganese transport regulator of Bacillus subtilis. Nat. Struct. Biol. 10 (2003) 652-657
25. Que Q., and Helmann J.D. Manganese homeostasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins. Mol. Microbiol. 35 (2000) 1454-1468
26. Schmitt M.P., Predich M., Doukhan L., Smith I., and Holmes R.K. Characterization of an iron-dependent regulatory protein (IdeR) of Mycobacterium tuberculosis as a functional homolog of the diphtheria toxin repressor (DtxR) from Corynebacterium diphtheriae. Infect. Immun. 63 (1995) 4284-4289
27. Manabe Y.C., Saviola B.J., Sun L., Murphy J.R., and Bishai W.R. Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor. Proc. Natl Acad. Sci. USA 96 (1999) 12844-12848
28. D'Aquino J.A., Tetenbaum-Novatt J., White A., Berkovitch F., and Ringe D. Mechanism of metal ion activation of the diphtheria toxin repressor DtxR. Proc. Natl Acad. Sci. USA 102 (2005) 18408-18413
29. Kraulis P.J. Molscript-a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24 (1991) 946-950
30. Fenn T.D., Ringe D., and Petsko G.A. POVScript+: a program for model and data visualization using persistence of vision ray-tracing. J. Appl. Crystallogr. 36 (2003) 944-947
31. Twigg P.D., Parthasarathy G., Guerrero L., Logan T.M., and Caspar D.L. Disordered to ordered folding in the regulation of diphtheria toxin repressor activity. Proc. Natl. Acad. Sci. USA 98 (2001) 11259-11264
32. Greenfield N.J. Using circular dichroism collected as a function of temperature to determine the thermodynamics of protein unfolding and binding interactions. Natl. Protoc. 1 (2006) 2527-2535
33. Tao X., Boyd J., and Murphy J.R. Specific binding of the diphtheria tox regulatory element DtxR to the tox operator requires divalent heavy metal ions and a 9-base-pair interrupted palindromic sequence. Proc. Natl Acad. Sci. USA 89 (1992) 5897-5901
34. Schmitt M.P., and Holmes R.K. Cloning, sequence, and footprint analysis of 2 promoter/operators from Corynebacterium diphtheriae that are regulated by the diphtheria toxin repressor (DtxR) and iron. J. Bacteriol. 176 (1994) 1141-1149
35. Otwinowski Z., and Minor W. Processing of X-ray Diffraction Data Collected in Oscillation Mode. Methods Enzymol. 276 (1997) 307-326
36. Evans G., and Pettifer R.F. CHOOCH: a program for deriving anomalous-scattering factors from X-ray fluorescence spectra. J. Appl. Crystallogr. 34 (2001) 82-86
37. McCoy A.J., Grosse-Kunstleve R.W., Storoni L.C., and Read R.J. Likelihood-enhanced fast translation functions. Acta Crystallogr., D Biol. Crystallogr. 61 (2005) 458-464
38. Brunger A.T., Adams P.D., Clore G.M., DeLano W.L., Gros P., Grosse-Kunstleve R.W., et al. Crystallography & NMR System: a new software suite for macromolecular structure determination. Acta Crystallogr., D Biol. Crystallogr. 54 (1998) 905-921
39. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr., D Biol. Crystallogr. 50 (1994) 760-763
40. Murshudov G.N., Vagin A.A., and Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr., D Biol. Crystallogr. 53 (1997) 240-255
41. Emsley P., and Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr., D Biol. Crystallogr. 60 (2004) 2126-2132
42. Brunger A.T. Free R-value-a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355 (1992) 472-475
43. Laskowski R.A., Macarthur M.W., Moss D.S., and Thornton J.M. Procheck-a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26 (1993) 283-291
44. Davis I.W., Leaver-Fay A., Chen V.B., Block J.N., Kapral G.J., Wang X., et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35 (2007) W375-W383