Discovery and characterization of a substrate selective p38α inhibitor

Biochemistry

Volumn 43, Issue 37, 2004, Pages 11658-11671

  Davidson, Walter ^a   Frego, Lee ^a   Peet, Gregory W ^a   Kroe, Rachel R ^a   Labadia, Mark E ^a   Lukas, Susan M ^a   Snow, Roger J ^a   Jakes, Scott ^a   Grygon, Christine A ^a   Pargellis, Christopher ^a   Werneburg, Brian G ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALORIMETRY; DEUTERIUM; ENZYME INHIBITION; HEAT TREATMENT; MASS SPECTROMETRY; SURFACE PLASMON RESONANCE;

DEUTERIUM EXCHANGE MASS SPECTROMETRY (DXMS); ISOTHERMAL TITRATION; PROTEIN KINASES;

ADENOSINETRIPHOSPHATE;

4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; COMPLEMENTARY DNA; CYTOKINE; DEUTERIUM; GLUTATHIONE TRANSFERASE; MAGNESIUM ION; MITOGEN ACTIVATED PROTEIN KINASE ACTIVATED PROTEIN KINASE 2; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE P38; PEPTIDE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ARTICLE; CALORIMETRY; CHEMICAL STRUCTURE; COMPETITIVE INHIBITION; DENATURATION; ENZYME INHIBITION; ENZYME KINETICS; ENZYME PHOSPHORYLATION; ENZYME SUBSTRATE; FLUORESCENCE; MASS SPECTROMETRY; PEPTIDE ANALYSIS; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STEADY STATE; SURFACE PLASMON RESONANCE;

ACTIVATING TRANSCRIPTION FACTOR 2; ADENOSINE TRIPHOSPHATE; AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; BIPHENYL COMPOUNDS; CALORIMETRY; CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN; ENZYME INHIBITORS; MICE; MITOGEN-ACTIVATED PROTEIN KINASE 14; MITOGEN-ACTIVATED PROTEIN KINASES; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN ISOFORMS; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES; SUBSTRATE SPECIFICITY; SURFACE PLASMON RESONANCE; TRANSCRIPTION FACTORS;

EID: 4644223114     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi0495073     Document Type: Article

References (44)

1. Dinarello, C. A. (1991) Inflammatory cytokines: interleukin-1 and tumor necrosis factor as effector molecules in autoimmune diseases, Curr. Opin. Immunol. 3, 941-948.
2. Feldmann, M., Brennan, F. M., and Maini, R. N. (1996) Role of cytokines in rheumatoid arthritis, Annu. Rev. Immunol. 14, 397-440.
3. Rankin, E. C., Choy, E. H., Kassimos, D., Kingsley, G. H., Sopwith, A. M., Isenberg, D. A., and Panayi, G. S. (1995) The therapeutic effects of an engineered human anti-tumor necrosis factor alpha antibody (CDP571) in rheumatoid arthritis, Br. J. Rheumatol. 34, 334-342.
4. Nuki, K. G., Bresnihan, B., Bear, M. B., and McCabe, D. (2002) Long-term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin-1 receptor antagonist) in patients with rheumatoid arthritis: extension phase of a randomized, double-blind, placebo-controlled trial, Arthritis Rheum. 46, 2838-2846.
5. Weinblatt, M. E., Kremer, J. M., Bankhurst, A. D., Bulpitt, K. J., Fleischmann, R. M., Fox, R. I., Jackson, C. G., Lange, M., and Burge, D. J. (1999) A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate, N. Engl. J. Med. 340, 253-259.
6. Jarvis, B., and Faulds, D. (1999) Etanercept: a review of its use in rheumatoid arthritis. Drugs 57, 945-966.
7. Lee, J. C., Badger, A. M., Griswold, D. E., Dunnington, D., Truneh, A., Votta, B., White, J. R., Young, P. R., and Bender, P. E. (1993) Bicyclic imidazoles as a novel class of cytokine biosynthesis inhibitors, Ann. N.Y. Acad. Sci. 696, 149-170.
8. Pargellis, C., Tong, L., Churchill, L., Cirillo, P. F., Gilmore, T., Graham, A. G., Grob, P. M., Mickey, E. R., Moss, N., Pav, S., and Regan, J. (2002) Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site, Nat. Struct. Biol. 9, 268-272.
9. -/- neutrophils in zigmond chambers containing formyl-methionyl-leuc-phenyalanine gradients, J. Immunol. 167, 3953-3961.
10. Kotlyarov, A., Yannani, Y., Fritz, S., Laass, K., Telliez, J.-B., Pitman, D., Liu, L.-L., and Gaestel, M. (2002) Distinct cellular functions of MK2, Mol. Cell Biol. 22, 4827-4835.
11. Kontonyiannis, D., Boulougouris, G., Manoloukos, M., Armaka, M., Apostoloki, M., Pizarro, T., Kotlyarov, A., Forster, I., Flavell, R., Gaestel, M., Tsichlis, P., Cominelli, F., and Kollias, G. (2002) Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn's-like inflammatory bowel disease, J. Exp. Med. 196, 1563-1574.
12. Wang, X., Xu, L., Wang, H., Young, P. R., Gaestel, M., and Feurstein, G. Z. (2002) Mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 deficiency protects brain from ischemic injury in mice, J. Biol. Chem. 277, 43968-43972.
13. Shi, Y., and Gaestel, M. (2002) In the cellular garden of forking paths: how p38 MAPKs signal for downstream assistance, Biol. Chem. 383, 1519-1536.
14. Tanoue, T., Moriguchi, A. M., and Nishida, E. (2000) A conserved docking motif in MAP kinases common to substrates, activators and regulators, Nat. Cell Biol. 2, 110-116.
15. Tanoue, T., Maeda, R., Adachi, M., and Nishida, E. (2001) Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions, EMBO J. 20, 466-479.
16. Wilson, K. P., Fitsgibbon, M. J., Caron, P. R., Griffith, J. P., Chen, W., McCaffrey, P. G., Chamber, S. P., and Su, M. (1996) Crystal structure of p38 mitogen-activated protein kinase, J. Biol. Chem. 271, 27696-27700.
17. Wang, Z., Harkins, P. C., Ulevitch, R. J., Han, J., Cobb, M. H., and Goldsmith, E. J. (1997) The structure of mitogen-activated protein kinase p38 at 2.1 Å resolution, Proc. Natl. Acad. Sci. U.S.A. 94, 2327-2332.
18. Chang, C., Xu, B., Akella, R., Cobb, M. H., and Goldsmith, E. J. (2002) Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b, Mol. Cell 9, 1241-1249.
19. Kotlyarov, A., Neininger, A., Schubert, C., Eckert, R., Birchmeier, C., Volk, H. D., and Gaestel, M. (1999) MAPKAP kinase 2 is essential for LPS-induced TNF-α biosynthesis, Nat. Cell Biol. 1, 94-97.
20. Lukas, S. M., Kroe, R. R., Wildeson, J., Peet, G. W., Frego, L., Davidson, W., Ingraham, R. H., Pargellis, C. A., Labadia, M. E., and Werneburg, B. G. (2004) Catalysis and function of the p38α· MK2a signaling complex, Biochemistry 43, 9950-9960.
21. Neiniger, A., Kontoyiannis, D., Kotlyarov, A., Winzen, R., Eckert, R., Volk, H. D., Holtmann, H., Kollias, G., and Gaestel, M. (2002) MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels, J. Biol. Chem. 277, 3065-3068.
22. Ben-Levy, R., Leighton, I. A., Doza, Y. N., Attwood, P., Morrice, N., Marshall, C. J., and Cohen, P. (1995) Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2, EMBO J. 14, 5920-5930.
23. Mahtani, K. R., Brook, M., Dean, J. L., Sully, G., Saklatvala, J., and Clark, A. R. (2001) Mitogen-activated protein kinase p38 controls the expression and posttranslational modification of tristetraprolin, a regulator of tumor necrosis factor alpha mRNA stability, Mol. Cell. Biol. 21, 6461-6469.
24. Ben-Levy, R., Hooper, S., Wilson, R., Peterson, H. F., and Marshall, C. J. (1998) Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2, Curr. Biol 8, 1049-1057.
25. Engel, K., Kotlyarov, A., and Gaestel, M. (1998) Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation, EMBO J. 17, 3363-3371.
26. Neineinger, A., Theilemann, H., and Gaestel, M. (2001) FRET-based detection of different conformations of MK2, EMBO Rep. 21, 703-708.
27. Zhang, Z. Q., and Smith, D. L. (1993) Determination of amide hydrogen exchange by mass spectrometry: A new tool for protein structure elucidation, Protein Sci. 2, 522-531.
28. Zhang, Z. Q., Post, C. B., and Smith, D. L. (1996) Amide hydrogen exchange determined by mass spectrometry: application to rabbit muscle aldolase, Biochemistry 35, 779-791.
29. Resing, K. A., and Ahn, N. G. (1998) Deuterium exchange mass spectrometry as a probe of protein kinase activation. Analysis of wild type and constitutively active mutants of MAP kinase kinase-1, Biochemistry 37, 463-475.
30. Resing, K. A., Hoofnagle, A. N., and Ahn, N. G. (1999) Modeling deuterium exchange behavior of ERK2 using peptide mapping to probe secondary structure, J. Am. Soc. Mass Spectrom. 10, 685-702.
31. Hoofnagle, A. N., Resing, K. A., Goldsmith, E. J., and Ahn, N. G. (2001) Changes in protein conformational mobility upon activation of extracellular regulated protein kinase-2 as detected by hydrogen exchange, Proc. Natl. Acad. Sci. U.S.A. 98, 956-961.
32. Ehring, H. (1999) Hydrogen exchange-electrospray ionization mass spectrometry studies of structural features of proteins and protein/ protein interactions, Anal. Biochem. 267, 252-259.
33. Englander, J. J., Del Mar, C., Englander, S. W., Kim, J. S., Stranz, D. D., Hamuro, Y., and Woods, V. (2003) Protein structure change studied by hydrogen-deuterium exchange, functional labeling and mass spectrometry, Proc. Natl. Acad. Sci. U.S.A. 100, 7057-7062.
34. Hamuro, Y., Wong, L., Shaffer, J., Kim, J. S., Stranz, D. D., Jennings, P. A., Woods, V. L., and Adam, J. A. J. (2002) Phosphorylation-driven motions in the COOH-terminal Src kinase, Csk, revealed by enhanced hydrogen-deuterium exchange and mass spectrometry, J. Mol. Biol. 3, 871-881.
35. Kroe, R. R., Regan, J., Proto, A., Peet, G. W., Roy, T., Landro, L. D., Fuschetto, N. G., Pargellis, C. A., and Ingraham, R. H. (2003) Thermal denaturation: a method to rank slow binding, high-affinity p38α MAP kinase inhibitors, J. Med. Chem. 46, 4669-4675.
36. LoGrasso, P. V., Frantz, B., Rolando, A. M., O'Keefe, S. J., Hermes, J. D., and O'Neill, E. A. (1997) Kinetic mechanism for p38 MAP kinase, Biochemistry 36, 10422-10427.
37. Frantz, B., Klatt, T., Pang, M., Parsons, J., Rolando, A., Williams, H., Tocci, M. J., O'Keefe, S. J., and O'Neil, E. A. (1998) The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding, Biochemistry 37, 13846-13853.
38. Meng, W., Swenson, L. L., Fitzgibbon, M. J., Hayakawa, K., Haar, E., Behrens, A. E., Fulghum, J. R., and Lippke, J. A. (2002) Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export, J. Biol. Chem. 277, 37401-37405.
39. Underwood, K. W., Parris, K. D., Federico, E., Mosyak, L., Czerwinski, R. M., Shane, T., Taylor, M., Svenson, K., Liu, Y., Hsiao, C.-L., Wolfrom, S., Maguire, M., Malakian, K., Telliez, J.-B., Lin, L.-L., Kriz, R. W., Seehra, J., Somers, W. S., and Stahl, M. L. (2003) Catalytically active MAP KAP kinase 2 structures in complex with staurosporine and ADP reveal differences with the autoinhibited enzyme, Structure 11, 627-636.
40. Lee, T., Hoofnagle, A. N., Kabuyama, Y., Stroud, J., Min, X., Goldsmith, E. J., Resing, K. A., and Ahn, N. G. (2004) Docking motif interactions in MAP kinases revealed by hydrogen exchange mass spectrometry, Mol. Cell 14, 43-55.
41. Tong, L., Pav, S., White, D. M., Rogers, S., Crane, K. M., Cywin, C. L., Brown, M. L., and Pargellis, C. A. (1997) A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket, Nat. Struct. Biol. 4, 311-316.
42. Bellon, S., Fitzgibbon, M. J., Fox, T., Hsiao, H.-M., and Wilson, K. P. (1999) The structure of phosphorylated p38γ is monomeric and reveals a conserved activation-loop conformation, Structure 7, 1057-1065.
43. Bossemeyer, D., Engh, R. A., Kinzel, V., Ponstingl, H., and Huber, R. (1993) Phosphotransferase and substrate binding mechanism of the cAMP-dependent protein kinase catalytic subunit from porcine heart as deduced from the 2.0 Å structure of the complex with manganese(2+) adenylyl imidodiphosphate and inhibitor peptide PKI(5-24), EMBO J. 12, 849-859.
44. 2+)-ATP-oxalate complex of the rabbit muscle pyruvate kinase at 2.1 Å resolution: ATP binding over a barrel, Biochemistry 37, 6247-6255.