Protein kinases as antibacterial targets

Current Opinion in Cell Biology

Volumn 21, Issue 2, 2009, Pages 325-330

  Schreiber, Mark ^a   Res, Ivica ^a   Matter, Alex ^a  

^a NOVARTIS INSTITUTE FOR TROPICAL DISEASES   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; AX 14585; AX 20017; AX 35510; MITOXANTRONE; PROTEIN HISTIDINE KINASE; PROTEIN HISTIDINE KINASE INHIBITOR; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE; UNCLASSIFIED DRUG; VI 12112;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; CYTOTOXICITY; DRUG INHIBITION; MINIMUM INHIBITORY CONCENTRATION; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW;

ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; DRUG DESIGN; DRUG RESISTANCE, MULTIPLE, BACTERIAL; HUMANS; MOLECULAR STRUCTURE; MYCOBACTERIUM TUBERCULOSIS; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; SIGNAL TRANSDUCTION;

BACTERIA (MICROORGANISMS); EUKARYOTA; MYCOBACTERIUM TUBERCULOSIS;

EID: 63749108581     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceb.2009.01.026     Document Type: Review

References (27)

1. Hynes N.E. Tyrosine kinase signalling in breast cancer. Breast Cancer Res 2 (2000) 154-157
2. Hynes N.E., and Boulay A. The mTOR pathway in breast cancer. J Mammary Gland Biol Neoplasia 11 (2006) 53-61
3. Capdeville R., Buchdunger E., Zimmermann J., and Matter A. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 1 (2002) 493-502
4. Fabbro D., Parkinson D., and Matter A. Protein tyrosine kinase inhibitors: new treatment modalities?. Curr Opin Pharmacol 2 (2002) 374-381
5. Cohen M.L. Changing patterns of infectious disease. Nature 406 (2000) 762-767
6. Walsh C. Molecular mechanisms that confer antibacterial drug resistance. Nature 406 (2000) 775-781
7. Szurmant H., White R.A., and Hoch J.A. Sensor complexes regulating two-component signal transduction. Curr Opin Struct Biol 17 (2007) 706-715. Excellent review of the two component signal transduction systems of bacteria and the structural mechanisms by which they function.
8. Bronner S., Monteil H., and Prevost G. Regulation of virulence determinants in Staphylococcus aureus: complexity and applications. FEMS Microbiol Rev 28 (2004) 183-200
9. Matsushita M., and Janda K.D. Histidine kinases as targets for new antimicrobial agents. Bioorg Med Chem 10 (2002) 855-867
10. Macielag M.J., and Goldschmidt R. Inhibitors of bacterial two-component signalling systems. Expert Opin Investig Drugs 9 (2000) 2351-2369
11. Hilliard J.J., Goldschmidt R.M., Licata L., Baum E.Z., and Bush K. Multiple mechanisms of action for inhibitors of histidine protein kinases from bacterial two-component systems. Antimicrob Agents Chemother 43 (1999) 1693-1699
12. Gilmour R., Foster J.E., Sheng Q., McClain J.R., Riley A., Sun P.M., Ng W.L., Yan D., Nicas T.I., Henry K., et al. New class of competitive inhibitor of bacterial histidine kinases. J Bacteriol 187 (2005) 8196-8200
13. Qin Z., Zhang J., Xu B., Chen L., Wu Y., Yang X., Shen X., Molin S., Danchin A., Jiang H., et al. Structure-based discovery of inhibitors of the YycG histidine kinase: new chemical leads to combat Staphylococcus epidermidis infections. BMC Microbiol 6 (2006) 96. The authors use modern computational approaches to design inhibitors of an interesting new antibacterial target.
14. Martin P.K., Li T., Sun D., Biek D.P., and Schmid M.B. Role in cell permeability of an essential two-component system in Staphylococcus aureus. J Bacteriol 181 (1999) 3666-3673
15. Fabret C., and Hoch J.A. A two-component signal transduction system essential for growth of Bacillus subtilis: implications for anti-infective therapy. J Bacteriol 180 (1998) 6375-6383
16. Qin Z., Lee B., Yang L., Zhang J., Yang X., Qu D., Jiang H., and Molin S. Antimicrobial activities of YycG histidine kinase inhibitors against Staphylococcus epidermidis biofilms. FEMS Microbiol Lett 273 (2007) 149-156
17. Kitayama T., Iwabuchi R., Minagawa S., Sawada S., Okumura R., Hoshino K., Cappiello J., and Utsumi R. Synthesis of a novel inhibitor against MRSA and VRE: preparation from zerumbone ring opening material showing histidine-kinase inhibition. Bioorg Med Chem Lett 17 (2007) 1098-1101
18. Wehenkel A., Bellinzoni M., Grana M., Duran R., Villarino A., Fernandez P., Andre-Leroux G., England P., Takiff H., Cervenansky C., et al. Mycobacterial Ser/Thr protein kinases and phosphatases: physiological roles and therapeutic potential. Biochim Biophys Acta 1784 (2008) 193-202. Relatively brief, but informative review of Mycobacterial Ser/Thr kinases and phosphatases. Also contains a section on the substrates of the kinases.
19. Fernandez P., Saint-Joanis B., Barilone N., Jackson M., Gicquel B., Cole S.T., and Alzari P.M. The Ser/Thr protein kinase PknB is essential for sustaining mycobacterial growth. J Bacteriol 188 (2006) 7778-7784
20. Wehenkel A., Fernandez P., Bellinzoni M., Catherinot V., Barilone N., Labesse G., Jackson M., and Alzari P.M. The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. FEBS Lett 580 (2006) 3018-3022
21. Walburger A., Koul A., Ferrari G., Nguyen L., Prescianotto-Baschong C., Huygen K., Klebl B., Thompson C., Bacher G., and Pieters J. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science 304 (2004) 1800-1804
22. Scherr N., Honnappa S., Kunz G., Mueller P., Jayachandran R., Winkler F., Pieters J., and Steinmetz M.O. Structural basis for the specific inhibition of protein kinase G, a virulence factor of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 104 (2007) 12151-12156. The authors report a crystal structure of PknG in complex with AX20017. The structure revealed that while the topology was similar to the eukaryotic kinases, the binding pocket contained a set of unique ligand-binding residues not found in human kinases.
23. Szekely R., Waczek F., Szabadkai I., Nemeth G., Hegymegi-Barakonyi B., Eros D., Szokol B., Pato J., Hafenbradl D., Satchell J., et al. A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling. Immunol Lett 116 (2008) 225-231. The novel approach of simultaneously targeting PknB and PknG is presented, reporting the inhibition data for some molecules of interest.
24. Keri G., Szekelyhidi Z., Banhegyi P., Varga Z., Hegymegi-Barakonyi B., Szantai-Kis C., Hafenbradl D., Klebl B., Muller G., Ullrich A., et al. Drug discovery in the kinase inhibitory field using the Nested Chemical Library technology. Assay Drug Dev Technol 3 (2005) 543-551
25. Garavaglia S., Raffaelli N., Finaurini L., Magni G., and Rizzi M. A novel fold revealed by Mycobacterium tuberculosis NAD kinase, a key allosteric enzyme in NADP biosynthesis. J Biol Chem 279 (2004) 40980-40986
26. Sassetti C.M., Boyd D.H., and Rubin E.J. Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48 (2003) 77-84
27. Hegymegi-Barakonyi B., Szekely R., Varga Z., Kiss R., Borbely G., Nemeth G., Banhegyi P., Pato J., Greff Z., Horvath Z., et al. Signalling inhibitors against Mycobacterium tuberculosis-early days of a new therapeutic concept in tuberculosis. Curr Med Chem 15 (2008) 2760-2770