What Glues a Homodimer Together: Systematic Analysis of the Stabilizing Effect of an Aromatic Hot Spot in the Protein-Protein Interface of the tRNA-Modifying Enzyme Tgt

ACS Chemical Biology

Volumn 10, Issue 8, 2015, Pages 1897-1907

  Jakobi, Stephan ^a   Nguyen, Phong T X ^a   Debaene, François ^b,c   Cianférani, Sarah ^b,c   Reuter, Klaus ^a   Klebe, Gerhard ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b UNIVERSITÉ DE STRASBOURG   (France)

^c CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC AMINO ACID; DIMER; GLYCOSYLTRANSFERASE; HOMODIMER; MONOMER; OLIGONUCLEOTIDE; TRANSFER RNA; WATER; QUEUINE TRNA-RIBOSYLTRANSFERASE;

ARTICLE; CONCENTRATION RESPONSE; CONFORMATION; CRYSTAL STRUCTURE; ENZYME KINETICS; HYDROGEN BOND; HYDROPHOBICITY; MASS SPECTROMETRY; NONHUMAN; PRIORITY JOURNAL; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; SHIGELLA; SITE DIRECTED MUTAGENESIS; WILD TYPE; CHEMICAL STRUCTURE; CHEMISTRY; ENZYMOLOGY; GENETICS; HUMAN; MICROBIOLOGY; POINT MUTATION; PROTEIN MULTIMERIZATION; PROTEIN STABILITY; SHIGELLOSIS; ZYMOMONAS;

SHIGELLA;

DYSENTERY, BACILLARY; HUMANS; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; PENTOSYLTRANSFERASES; POINT MUTATION; PROTEIN MULTIMERIZATION; PROTEIN STABILITY; SHIGELLA; ZYMOMONAS;

EID: 84939789031     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/acschembio.5b00028     Document Type: Article

References (58)

1. Arkin, M. R. and Wells, J. A. (2004) Small-molecule inhibitors of protein-protein interactions: progressing towards the dream Nat. Rev. Drug. Discovery 3, 301-317
2. Wells, J. A. and McClendon, C. (2007) Reaching for high-hanging fruit in drug discovery at protein-protein interfaces Nature 450, 1001-1009
3. Morelli, X., Bourgeas, R., and Roche, P. (2011) Chemical and structural lessons from recent successes in protein-protein interaction inhibition (2P2I) Curr. Opin. Chem. Biol. 18, 475-481
4. Stumpf, M., Thorne, T., de Silva, E., Stewart, R., An, H., Lappe, M., and Wiuf, C. (2008) Estimating the size of the human interactome Proc. Natl. Acad. Sci. U.S.A. 105, 6959-6964
5. Zinzalla, G. and Thurston, D. E. (2009) Targeting protein-protein interactions for therapeutic intervention, a challenge for the future Future Med. Chem. 1, 65-93
6. Mayer, B. J. (1999) Protein-protein interactions in signaling cascades Mol. Biotechnol. 13, 201-213
7. Keskin, O., Ma, B., and Nussinov, R. (2005) Hot regions in protein-protein interactions, the organization and contribution of structurally conserved hot spot residues J. Mol. Biol. 345, 1281-1294
8. Moreira, I. S., Fernandes, P. A., and Ramos, M. J. (2007) Hot spots-A review of the protein-protein interface determinant amino-acid residues Proteins: Struct., Funct., Bioinf. 68, 803-812
9. Wells, J. A. (1991) Systematic mutational analyses of protein-protein interfaces Methods Enzymol. 202, 390-411
10. Cunningham, B. and Wells, J. A. (1989) High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis Science 244, 1081-1085
11. Clackson, T. and Wells, J. A. (1995) A hot spot of binding energy in a hormone-receptor interface Science 267, 383-386
12. Berg, T. (2003) Modulation of protein-protein interactions with small organic molecules Angew. Chem., Int. Ed. 42, 2462-2481
13. Yin, H. and Hamilton, A. D. (2005) Strategies for targeting protein-protein interactions with synthetic agents Angew. Chem., Int. Ed. 44, 4130-4163
14. Che, Y., Brooks, B. R., and Marschall, G. R. (2006) Development of small molecules designed to modulate protein-protein interactions J. Comput.-Aided Mol. Des. 20, 109-130
15. Jakobi, S., Nguyen, T. X. P., Debaene, F., Metz, A., Sanglier-Cianférani, S., Reuter, K., and Klebe, G. (2014) Hot spot analysis to dissect the functional protein-protein interface of a tRNA-modifying enzyme Proteins: Struct., Funct., Bioinf. 82, 2713-32
16. Stengl, B., Meyer, E. A., Heine, A., Brenk, R., Diederich, F., and Klebe, G. (2007) Crystal structures of tRNA-guanine transglycosylase (TGT) in complex with novel and potent inhibitors unravel pronounced induced-fit adaptations and suggest dimer formation upon substrate binding J. Mol. Biol. 370, 492-511
17. Ritschel, T., Atmanene, C., Reuter, K., Van Dorsselaer, A., Sanglier-Cianferani, S., and Klebe, G. (2009) An integrative approach combining noncovalent mass spectrometry, enzyme kinetics and X-ray crystallography to decipher Tgt protein-protein and protein-RNA interaction J. Mol. Biol. 393, 833-847
18. Xie, W., Liu, X., and Huang, R. H. (2003) Chemical trapping and crystal structure of a catalytic tRNA guanine transglycosylase covalent intermediate Nat. Struct. Biol. 10, 781-788
19. Hoertner, S. R., Ritschel, T., Stengl, B., Kramer, C., Schweizer, W. B., Wagner, B., Kansy, M., Klebe, G., and Diederich, F. (2005) Potent inhibitors of tRNA-guanine transglycosylase, an enzyme linked to the pathogenicity of the Shigella bacterium, charge-assisted hydrogen bonding Angew. Chem., Int. Ed. 45, 8266-8269
20. Stengl, B., Reuter, K., and Klebe, G. (2005) Mechanism and substrate specificity of tRNA-guanine transglycosylases (TGTs), tRNA modifying enzymes from thee three different kingdoms of life seem to share a common mechanism ChemBioChem 6, 1-15
21. Boland, C., Hayes, P., Santa-Maria, I., Nishimura, S., and Kelly, V. P. (2009) Queuosine formation in eucaryotic tRNA occurs via a mitochondria-localized heteromeric transglycosylase J. Biol. Chem. 284, 18218-27
22. Chen, V.-C., Kelly, V. P., Stachura, S. V., and Garcia, G. A. (2010) Characterization of the human tRNA-guanine transglycosylase, confirmation of the heterodimeric subunit structure RNA 16, 958-968
23. Immekus, F., Barandun, L. J., Betz, M., Debaene, F., Petiot, S., Sanglier-Cianferani, S., Reuter, K., Diederich, F., and Klebe, G. (2013) Launching spiking ligands into a protein-protein interface: a promising strategy to destabilize and break interface formation in a tRNA modifying enzyme ACS Chem. Biol. 8, 1163-1178
24. Bogan, A. A. and Thorn, K. S. (1998) Anatomy of hot spots in protein interfaces J. Mol. Biol. 280, 1-9
25. Jakobi, S. (2013) Ph.D. Thesis, University of Marburg.
26. Thorn, K. S. and Bogan, A. A. (2001) ASEdb, A database of alanine mutations and their effects on the free energy of binding in protein interactions Bioinformatics 17, 284-85
27. Glaser, F., Steinberg, D. M., Vakser, I. A., and Ben-Tal, N. (2001) Residue frequencies and pairing preferences at protein-protein interfaces Proteins: Struct., Funct., Genet. 43, 89-102
28. Yan, C., Wu, F., Jernigan, R. L., Dobbs, D., and Honavar, V. (2008) Characterization of protein-protein interfaces Protein J. 27, 59-70
29. Keskin, O., Ma, B., and Nussinov, R. (2005) Hot regions in protein-protein interactions, the organization and contribution of structurally conserved hot spot residues J. Mol. Biol. 345, 1281-1294
30. Bahadur, R. P., Chakrabarti, P., Rodier, F., and Janin, J. (2003) Dissecting subunit interfaces in homodimeric proteins Proteins: Struct., Funct., Genet 53, 708-719
31. Saha, R. P., Bhattacharyya, R., and Chakrabarti, P. (2007) Interaction geometry involving planar groups in protein-protein interfaces Proteins: Struct., Funct., Bioinf. 67, 84-97
32. Moreira, I. S., Fernandes, P. A., and Ramos, M. J. (2007) Hot spots-a review of the protein-protein interface determinant amino-acid residues Proteins: Struct., Funct., Bioinf. 68, 803-812
33. Bhattacharyya, R., Saha, R. P., Samanta, U., and Chakrabarti, P. (2003) Geometry of interaction of the histidine ring with other planar and basic residues J. Proteome Res. 2, 255-263
34. Moreira, I. S., Martins, J. M., Ramos, R. M., Fernandes, P. A., and Ramos, M. J. (2013) Understanding the importance of the aromatic amino-acid residues as hot-spots Biochim. Biophys. Acta 1834, 404-414
35. Espinoza-Fonseca, L. M. (2012) Aromatic residues link binding and function of intrinsically disordered proteins Mol. BioSyst. 8, 237-46
36. Padlan, E. A. (1990) On the nature of antibody combining sites, unusual structural features that may confer on these sites an enhanced capacity for binding ligands Proteins: Struct., Funct., Genet. 7, 112-124
37. Davies, D. R. and Cohen, G. H. (1996) Interactions of protein antigens with antibodies Proc. Natl. Acad. Sci. U.S.A. 93, 7-12
38. Salonen, L. M., Ellermann, M., and Diederich, F. (2011) Aromatic rings in chemical and biological recognition, energetics and structures Angew. Chem. In.t Ed. 50, 4808-4842
39. Killian, J. A. and von Heijne, G. (2000) How proteins adapt to a membrane-water interface Trends in Biol. Sci. 25, 429-434
40. Ma, B. and Nussinov, R. (2007) Trp/Met/Phe hot spots in protein-protein interactions, potential targets in drug design Curr. Top. Med. Chem. 7, 999-1005
41. Bahadur, R. P., Chakrabarti, P., Rodier, F., and Janin, J. (2004) A dissection of specific and non-specific protein-protein interfaces J. Mol. Biol. 336, 943-955
42. Janin, J. (1997) Specific vs non-specific contacts in protein crystals Nat. Struct. Biol. 4, 973-974
43. Ponstingl, H., Henrick, K., and Thornton, J. M. (2000) Discriminating between homodimeric and monomeric proteins in the crystalline state Proteins: Struct., Funct., Bioinf. 41, 47-57
44. Tsuchiya, Y., Nakamura, H., and Kinoshita, K. (2008) Discrimination between biological interfaces and crystal-packing contacts Adv. Appl. Bioinf. Chem. 1, 99-113
45. Dasgupta, S., Iyer, G., Bryant, S., Lawrence, C., and Bell, J. (1997) Extent and nature of contacts between protein molecules in crystal lattices and between subunits of protein oligomers Proteins: Struct., Funct., Genet. 28, 494-514
46. Janin, J. (1999) Wet and dry interfaces: the role of solvent in protein-protein and protein-DNA recognition Structure 7, R277-R279
47. Moreira, I. S., Fernandes, P. A., and Ramos, M. J. (2007) Hot spots occlusion from bulk water-a comprehensive study of the complex between the lyzozyme HEL and the antibody FVD1.3 J. Phys. Chem. B 111, 2697-2706
48. Cho, K. I., Lee, K., Lee, K. H., Kim, D., and Lee, D. (2006) Specificity of molecular interactions in transient protein-protein interaction interfaces Proteins: Struct., Funct., Bioinf. 65, 593-606
49. Biela, I., Tidten-Luksch, N., Immekus, F., Glinca, S., Nguyen, T. X. P., Gerber, H.-D., Heine, A., Klebe, G., and Reuter, K. (2013) Investigation of specificity determinants in bacterial tRNA-guanine transglycosylase reveals queuine, the substrate of its eucaryotic counterpart, as inhibitor PLoS One 8, e64240
50. Curnow, A., Kung, F. L., Koch, K. A., and Garcia, G. A. (1993) tRNA-guanine transglycosylase from Escherichia coli, gross tRNA structural requirements for recognition Biochemistry 32, 5239-5246
51. Mueller, U., Darowski, N., Fuchs, M. R., Förster, R., Hellmig, M., Paithankar, K. S., Pühringer, S., Steffien, M., Zocher, G., and Weiss, M. S. (2012) Facilities for macromolecular crystallography at the Helmholtz-Zentrum Berlin J. Synchrotron Radiat. 19, 442-449
52. Otwinowski, Z. and Minor, W. (1997) Processing of X-ray diffraction data collected in oscillation mode Methods Enzymol. 276, 307-326
53. Romier, C., Reuter, K., Suck, D., and Ficner, R. (1996) Crystal structure of tRNA-guanine transglycosylase: RNA modification by base exchange EMBO J. 15, 2850-2857
54. McCoy, A., Grosse-Kunstleve, R., Adams, P., Winn, M., Storoni, L., and Read, R. (2007) Phaser crystallographic software J. Appl. Crystallogr. 40, 658-674
55. Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P., Keegan, R., Krissinel, E., Leslie, A., McCoy, S., McNicholas, S., Mershudov, G., Pannu, N., Potterton, E., Powell, H., Read, R., Vagin, A., and Wilson, K. (2011) Overview of the CCP4 suite and current developments Acta Crystallogr., Sect. D: Biol. Crystallogr. 67, 235-242
56. Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., EchooIs, N., Headd, J., Hung, L.-W., Kapral, G., Grosse-Kunstleve, R., McCoy, A., Moriarty, N., Oeffner, R., Read, R., Richardson, D., Richardson, J., Terwilliger, T., and Zwart, P. (2010) PHENIX, a comprehensive Python-based system for macromolecular structure solution Acta Crystallogr., Sect. D: Biol. Crystallogr. 66, 213-221
57. Emsley, P. and Cowtan, K. (2004) Coot, model-building tools for molecular graphics Acta Crystallogr., Sect. D: Biol. Crystallogr. 60, 2126-2132
58. Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., and Bourne, P. E. (2000) The Protein Data Bank Nucleic Acids Res. 28, 235-242