Structure-guided optimization of protein kinase inhibitors reverses aminoglycoside antibiotic resistance

Biochemical Journal

Volumn 454, Issue 2, 2013, Pages 191-200

  Stogios, Peter J ^a,b   Spanogiannopoulos, Peter ^b,c   Evdokimova, Elena ^a,b   Egorova, Olga ^a   Shakya, Tushar ^b,c   Todorovic, Nick ^b,c   Capretta, Alfredo ^b,c   Wright, Gerard D ^b,c   Savchenko, Alexei ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

^c MCMASTER UNIVERSITY   (Canada)

Author keywords

Aminoglycoside phosphotransferase APH(3') Ia; Antibiotic resistance; Crystal structure; Protein kinase inhibitor; Structure based drug design

Indexed keywords

4 (3 CHLOROANILINO) 6,7 DIMETHOXYQUINAZOLINE; ADENOSINE TRIPHOSPHATASE (CALCIUM); AMINOGLYCOSIDE ANTIBIOTIC AGENT; APH(3') IA; KANAMYCIN; PROTEIN KINASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL STRAIN; CROSS REACTION; CRYSTALLIZATION; DRUG DESIGN; ESCHERICHIA COLI; IN VITRO STUDY; INHIBITION KINETICS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PURIFICATION; SYNTHESIS; X RAY DIFFRACTION;

ACINETOBACTER BAUMANNII; AMINOGLYCOSIDES; ANTHRACENES; ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; BINDING SITES; DRUG DESIGN; DRUG RESISTANCE, BACTERIAL; ESCHERICHIA COLI; ISOENZYMES; KANAMYCIN; KANAMYCIN KINASE; MICROBIAL SENSITIVITY TESTS; MOLECULAR CONFORMATION; PROTEIN KINASE INHIBITORS; PYRAZOLES; PYRIMIDINES; QUINAZOLINES; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84881537568     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20130317     Document Type: Article

References (52)

1. Arias, C. A. and Murray, B. E. (2009) Antibiotic-resistant bugs in the 21st century: a clinical super-challenge. N. Engl. J. Med. 360, 439-443
2. Morar, M. and Wright, G. D. (2010) The genomic enzymology of antibiotic resistance. Annu. Rev. Genet. 44, 25-51
3. Boucher, H. W., Talbot, G. H., Bradley, J. S., Edwards, J. E., Gilbert, D., Rice, L. B., Scheld, M., Spellberg, B. and Bartlett, J. (2009) Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48, 1-12
4. Fischbach, M. A. and Walsh, C. T. (2009) Antibiotics for emerging pathogens. Science 325, 1089-1093
5. Ejim, L., Farha, M. A., Falconer, S. B., Wildenhain, J., Coombes, B. K., Tyers, M., Brown, E. D. and Wright, G. D. (2011) Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy. Nat. Chem. Biol. 7, 348-350
6. Kalan, L. and Wright, G. D. (2011) Antibiotic adjuvants: multicomponent anti-infective strategies. Expert Rev. Mol. Med. 13, e5
7. Drawz, S. M. and Bonomo, R. A. (2010) Three decades of β-lactamase inhibitors. Clin. Microbiol. Rev. 23, 160-201
8. Wright, G. D. (2011) Molecular mechanisms of antibiotic resistance. Chem. Commun. 47, 4055-4061
9. Woodford, N., Turton, J. F. and Livermore, D. M. (2011) Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol. Rev. 35, 736-755
10. Shakya, T. and Wright, G. D. (2010) Nucleotide selectivity of antibiotic kinases. Antimicrob. Agents Chemother. 54, 1909-1913
11. Toth, M., Chow, J. W., Mobashery, S. and Vakulenko, S. B. (2009) Source of phosphate in the enzymic reaction as a point of distinction among aminoglycoside 2-phosphotransferases. J. Biol. Chem. 284, 6690-6696
12. Shi, K. and Berghuis, A. M. (2012) Structural basis for dual nucleotide selectivity of aminoglycoside 2-phosphotransferase IVa provides insight on determinants of nucleotide specificity of aminoglycoside kinases. J. Biol. Chem. 287, 13094-13102
13. Fong, D. H., Xiong, B., Hwang, J. and Berghuis, A. M. (2011) Crystal structures of two aminoglycoside kinases bound with a eukaryotic protein kinase inhibitor. PLoS ONE 6, e19589
14. Stogios, P. J., Shakya, T., Evdokimova, E., Savchenko, A. and Wright, G. D. (2011) Structure and function of APH(4)-Ia, a hygromycin B resistance enzyme. J. Biol. Chem. 286, 1966-1975
15. Toth, M., Frase, H., Antunes, N. T., Smith, C. A. and Vakulenko, S. B. (2010) Crystal structure and kinetic mechanism of aminoglycoside phosphotransferase-2-IVa. Protein Sci. 19, 1565-1576
16. Fong, D. H., Lemke, C. T., Hwang, J., Xiong, B. and Berghuis, A. M. (2010) Structure of the antibiotic resistance factor spectinomycin phosphotransferase from Legionella pneumophila . J. Biol. Chem. 285, 9545-9555
17. Fong, D. H. and Berghuis, A. M. (2009) Structural basis of APH(3)-IIIa-mediated resistance to N1-substituted aminoglycoside antibiotics. Antimicrob. Agents Chemother. 53, 3049-3055
18. Young, P. G., Walanj, R., Lakshmi, V., Byrnes, L. J., Metcalf, P., Baker, E. N., Vakulenko, S. B. and Smith, C. A. (2009) The crystal structures of substrate and nucleotide complexes of Enterococcus faecium aminoglycoside-2- phosphotransferase-IIa [APH(2)-IIa] provide insights into substrate selectivity in the APH(2) subfamily. J. Bacteriol. 191, 4133-4143
19. Nurizzo, D., Shewry, S. C., Perlin, M. H., Brown, S. A., Dholakia, J. N., Fuchs, R. L., Deva, T., Baker, E. N. and Smith, C. A. (2003) The crystal structure of aminoglycoside-3-phosphotransferase-IIa, an enzyme responsible for antibiotic resistance. J. Mol. Biol. 327, 491-506
20. Fong, D. H. and Berghuis, A. M. (2002) Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry. EMBO J. 21, 2323-2331
21. Burk, D. L., Hon, W. C., Leung, A. K. and Berghuis, A. M. (2001) Structural analyses of nucleotide binding to an aminoglycoside phosphotransferase. Biochemistry 40, 8756-8764
22. Hon, W. C., McKay, G. A., Thompson, P. R., Sweet, R. M., Yang, D. S., Wright, G. D. and Berghuis, A. M. (1997) Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases. Cell 89, 887-895
23. Liao, J. J.-L. (2007) Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors. J. Med. Chem. 50, 409-424
24. Shakya, T., Stogios, P. J., Waglechner, N., Evdokimova, E., Ejim, L., Blanchard, J. E., McArthur, A. G., Savchenko, A. and Wright, G. D. (2011) A small molecule discrimination map of the antibiotic resistance kinome. Chem. Biol. 18, 1591-1601
25. Oka, A., Sugisaki, H. and Takanami, M. (1981) Nucleotide sequence of the kanamycin resistance transposon Tn903. J. Mol. Biol. 147, 217-226
26. Vakulenko, S. B. and Mobashery, S. (2003) Versatility of aminoglycosides and prospects for their future. Clin. Microbiol. Rev. 16, 430-450
27. Siregar, J. J., Miroshnikov, K. and Mobashery, S. (1995) Purification, characterization, and investigation of the mechanism of aminoglycoside 3-phosphotransferase type Ia. Biochemistry 34, 12681-12688
28. Minor, W., Cymborowski, M., Otwinowski, Z. and Chruszcz, M. (2006) HKL-3000: the integration of data reduction and structure solution-from diffraction images to an initial model in minutes. Acta Crystallogr., Sect. D: Biol. Crystallogr. 62, 859-866
29. Kabsch, W. (2010) XDS. Acta Crystallogr., Sect. D: Biol. Crystallogr. 66, 125-132
30. Evans, P. (2006) Scaling and assessment of data quality. Acta Crystallogr., Sect. D: Biol. Crystallogr. 62, 72-82
31. Langer, G., Cohen, S. X., Lamzin, V. S. and Perrakis, A. (2008) Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7. Nat. Protoc. 3, 1171-1179
32. Murshudov, G. N., Vagin, A. A. and Dodson, E. J. (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr., Sect. D: Biol. Crystallogr. 53, 240-255
33. Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L. W., Kapral, G. J., Grosse-Kunstleve, R. W. et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr., Sect. D: Biol. Crystallogr. 66, 213-221
34. Painter, J. and Merritt, E. A. (2006) TLSMDweb server for the generation of multi-group TLS models. J. Appl. Crystallogr. 39, 109-111
35. Emsley, P. and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr., Sect. D: Biol. Crystallogr. 60, 2126-2132
36. Schindler, T., Sicheri, F., Pico, A., Gazit, A., Levitzki, A. and Kuriyan, J. (1999) Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor. Mol. Cell 3, 639-648
37. Apsel, B., Blair, J. A., Gonzalez, B., Nazif, T. M., Feldman, M. E., Aizenstein, B., Hoffman, R., Williams, R. L., Shokat, K. M. and Knight, Z. A. (2008) Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat. Chem. Biol. 4, 691-699
38. Lawrence, M. C. and Colman, P. M. (1993) Shape complementarity at protein/protein interfaces. J. Mol. Biol. 234, 946-950
39. Krissinel, E. and Henrick, K. (2007) Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797
40. Todorovic, N., Awuah, E., Shakya, T., Wright, G. D. and Capretta, A. (2011) Microwave-assisted synthesis of N1- and C3-substituted pyrazolo[3,4-d]pyrimidine libraries. Tetrahedron Lett. 52, 5761-5763
41. Cer, R. Z., Mudunuri, U., Stephens, R. and Lebeda, F. J. (2009) IC50-to-K i: a web-based tool for converting IC50 to K i values for inhibitors of enzyme activity and ligand binding. Nucleic Acids Res. 37, W441-W445
42. Thompson, P. R., Boehr, D. D., Berghuis, A. M. and Wright, G. D. (2002) Mechanism of aminoglycoside antibiotic kinase APH(3)-IIIa: role of the nucleotide positioning loop. Biochemistry 41, 7001-7007
43. Heo, Y.-S., Kim, S.-K., Seo, C. I., Kim, Y. K., Sung, B.-J., Lee, H. S., Lee, J. I., Park, S.-Y., Kim, J. H., Hwang, K. Y. et al. (2004) Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125. EMBO J. 23, 2185-2195
44. Scapin, G., Patel, S. B., Lisnock, J., Becker, J. W. and LoGrasso, P. V. (2003) The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity. Chem. Biol. 10, 705-712
45. Chu, M. L. H., Chavas, L. M. G., Douglas, K. T., Eyers, P. A. and Tabernero, L. (2008) Crystal structure of the catalytic domain of the mitotic checkpoint kinase Mps1 in complex with SP600125. J. Biol. Chem. 283, 21495-21500
46. Levitzki, A. and Mishani, E. (2006) Tyrphostins and other tyrosine kinase inhibitors. Annu. Rev. Biochem. 75, 93-109
47. Blencke, S., Zech, B., Engkvist, O., Greff, Z., Orfi, L., Horváth, Z., Kéri, G., Ullrich, A. and Daub, H. (2004) Characterization of a conserved structural determinant controlling protein kinase sensitivity to selective inhibitors. Chem. Biol. 11, 691-701
48. Knowles, P. P., Murray-Rust, J., Kjaer, S., Scott, R. P., Hanrahan, S., Santoro, M., Ibáñez, C. F. and McDonald, N. Q. (2006) Structure and chemical inhibition of the RET tyrosine kinase domain. J. Biol. Chem. 281, 33577-33587
49. Liu, Y., Bishop, A., Witucki, L., Kraybill, B., Shimizu, E., Tsien, J., Ubersax, J., Blethrow, J., Morgan, D. O. and Shokat, K. M. (1999) Structural basis for selective inhibition of Src family kinases by PP1. Chem. Biol. 6, 671-678
50. Ojo, K. K., Larson, E. T., Keyloun, K. R., Castaneda, L. J., Derocher, A. E., Inampudi, K. K., Kim, J. E., Arakaki, T. L., Murphy, R. C., Zhang, L. et al. (2010) Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nat. Struct. Mol. Biol. 17, 602-607
51. Liu, A., Tran, L., Becket, E., Lee, K., Chinn, L., Park, E., Tran, K. and Miller, J. H. (2010) Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code. Antimicrob. Agents Chemother. 54, 1393-1403
52. Bishop, A. C., Ubersax, J. A., Petsch, D. T., Matheos, D. P., Gray, N. S., Blethrow, J., Shimizu, E., Tsien, J. Z., Schultz, P. G., Rose, M. D. et al. (2000) A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature 407, 395-401 Diseases