Crystal structure of G protein-coupled receptor kinase 5 in complex with a rationally designed inhibitor

Journal of Biological Chemistry

Volumn 290, Issue 34, 2015, Pages 20649-20659

  Homan, Kristoff T ^a   Waldschmidt, Helen V ^a   Glukhova, Alisa ^a   Cannavo, Alessandro ^b   Song, Jianliang ^b   Cheung, Joseph Y ^b   Koch, Walter J ^b   Larsen, Scott D ^a   Tesmer, John J G ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

^b TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; BIOLOGICAL MEMBRANES; CELL SIGNALING; CURRICULA; ENZYMES; HYDROGEN BONDS; PROTEINS;

AMIDE SIDE CHAIN; C-TERMINAL REGIONS; CARDIO-VASCULAR DISEASE; G PROTEIN COUPLED RECEPTORS; G PROTEIN-COUPLED RECEPTOR KINASE; KINETIC PROPERTIES; STRUCTURE BASED DRUG DESIGNS; THERAPEUTIC DRUGS;

CRYSTAL STRUCTURE;

CCG 215022; G PROTEIN COUPLED RECEPTOR KINASE 5; PAROXETINE; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG; CARDIOVASCULAR AGENT; CCG215022; ENZYME INHIBITOR; PYRIDINE DERIVATIVE;

ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; COMPLEX FORMATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME CONFORMATION; HEART MUSCLE CELL; HYDROGEN BOND; HYDROPHOBICITY; MOUSE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; BOVINE; CARDIAC MUSCLE CELL; CHEMICAL PHENOMENA; CHEMICAL STRUCTURE; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; ENZYMOLOGY; GENE EXPRESSION; GENETICS; HEART CONTRACTION; HEART SEPTUM; HEART VENTRICLE; ISOLATION AND PURIFICATION; KINETICS; MOLECULAR GENETICS; MUTATION; PROTEIN DOMAIN; PROTEIN SECONDARY STRUCTURE; SEQUENCE ALIGNMENT; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

MURINAE;

ANIMALS; CARDIOVASCULAR AGENTS; CATALYTIC DOMAIN; CATTLE; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME INHIBITORS; G-PROTEIN-COUPLED RECEPTOR KINASE 5; GENE EXPRESSION; HEART SEPTUM; HEART VENTRICLES; HYDROGEN BONDING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; KINETICS; MICE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; MYOCARDIAL CONTRACTION; MYOCYTES, CARDIAC; PAROXETINE; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN STRUCTURE, SECONDARY; PYRIDINES; SEQUENCE ALIGNMENT;

EID: 84939611234     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.647370     Document Type: Article

References (52)

1. Ferguson, S. S. (2001) Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol. Rev. 53, 1-24
2. Gurevich, E. V., Tesmer, J. J., Mushegian, A., and Gurevich, V. V. (2012) G protein-coupled receptor kinases: more than just kinases and not only for GPCRs. Pharmacol. Ther. 133, 40-69
3. Fredericks, Z. L., Pitcher, J. A., and Lefkowitz, R. J. (1996) Identification of the G protein-coupled receptor kinase phosphorylation sites in the human beta2-adrenergic receptor. J. Biol. Chem. 271, 13796-13803
4. Liggett, S. B., Ostrowski, J., Chesnut, L. C., Kurose, H., Raymond, J. R., Caron, M. G., and Lefkowitz, R. J. (1992) Sites in the third intracellular loop of the α2A-adrenergic receptor confer short term agonist-promoted desensitization. Evidence for a receptor kinase-mediated mechanism. J. Biol. Chem. 267, 4740-4746
5. Gurevich, V. V., and Gurevich, E. V. (2006) The structural basis of arrestin-mediated regulation of G-protein-coupled receptors. Pharmacol. Ther. 110, 465-502
6. Mushegian, A., Gurevich, V. V., and Gurevich, E. V. (2012) The origin and evolution of G protein-coupled receptor kinases. PLoS One 7, e33806
7. Tesmer, J. J. (2009) Structure and function of regulator of G protein signaling homology domains. Prog. Mol. Biol. Transl. Sci. 86, 75-113
8. Carman, C. V., Barak, L. S., Chen, C., Liu-Chen, L. Y., Onorato, J. J., Kennedy, S. P., Caron, M. G., and Benovic, J. L. (2000) Mutational analysis of Gβγ and phospholipid interaction with G protein-coupled receptor kinase 2. J. Biol. Chem. 275, 10443-10452
9. Thiyagarajan, M. M., Stracquatanio, R. P., Pronin, A. N., Evanko, D. S., Benovic, J. L., and Wedegaertner, P. B. (2004) A predicted amphipathic helix mediates plasma membrane localization of GRK5. J. Biol. Chem. 279, 17989-17995
10. Yang, P., Glukhova, A., Tesmer, J. J., and Chen, Z. (2013) Membrane orientation and binding determinants of G protein-coupled receptor kinase 5 as assessed by combined vibrational spectroscopic studies. PLoS One 8, e82072
11. Pronin, A. N., Carman, C. V., and Benovic, J. L. (1998) Structure-function analysis of G protein-coupled receptor kinase-5. Role of the carboxyl terminus in kinase regulation. J. Biol. Chem. 273, 31510-31518
12. Lodowski, D. T., Pitcher, J. A., Capel, W. D., Lefkowitz, R. J., and Tesmer, J. J. (2003) Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gβγ. Science 300, 1256-1262
13. Boguth, C. A., Singh, P., Huang, C. C., and Tesmer, J. J. (2010) Molecular basis for activation of G protein-coupled receptor kinases. EMBO J. 29, 3249-3259
14. 2+-binding proteins on G protein-coupled receptor kinases. Biochemistry 37, 13650-13659
15. q-activating hypertrophic ligands is a calmodulin-dependent process. PLoS One 8, e57324
16. Rockman, H. A., Choi, D. J., Rahman, N. U., Akhter, S. A., Lefkowitz, R. J., and Koch, W. J. (1996) Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 93, 9954-9959
17. Chen, E. P., Bittner, H. B., Akhter, S. A., Koch, W. J., and Davis, R. D. (2001) Myocardial function in hearts with transgenic overexpression of the G protein-coupled receptor kinase 5. Ann. Thorac. Surg. 71, 1320-1324
18. Martini, J. S., Raake, P., Vinge, L. E., DeGeorge, B. R., Jr., DeGeorge, B., Jr., Chuprun, J. K., Harris, D. M., Gao, E., Eckhart, A. D., Pitcher, J. A., and Koch, W. J. (2008) Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes. Proc. Natl. Acad. Sci. U.S.A. 105, 12457-12462
19. Johnson, L. R., Scott, M. G., and Pitcher, J. A. (2004) G protein-coupled receptor kinase 5 contains a DNA-binding nuclear localization sequence. Mol. Cell. Biol. 24, 10169-10179
20. Yi, X. P., Gerdes, A. M., and Li, F. (2002) Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure-prone rats. Hypertension 39, 1058-1063
21. Yi, X. P., Zhou, J., Baker, J., Wang, X., Gerdes, A. M., and Li, F. (2005) Myocardial expression and redistribution of GRKs in hypertensive hypertrophy and failure. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 282, 13-23
22. Homan, K. T., Glukhova, A., and Tesmer, J. J. (2013) Regulation of G protein-coupled receptor kinases by phospholipids. Curr. Med. Chem. 20, 39-46
23. Huang, C. C., Yoshino-Koh, K., and Tesmer, J. J. (2009) A surface of the kinase domain critical for the allosteric activation of G protein-coupled receptor kinases. J. Biol. Chem. 284, 17206-17215
24. Warne, T., Serrano-Vega, M. J., Baker, J. G., Moukhametzianov, R., Edwards, P. C., Henderson, R., Leslie, A. G., Tate, C. G., and Schertler, G. F. (2008) Structure of a β1-adrenergic G-protein-coupled receptor. Nature 454, 486-491
25. Thal, D. M., Homan, K. T., Chen, J., Wu, E. K., Hinkle, P. M., Huang, Z. M., Chuprun, J. K., Song, J., Gao, E., Cheung, J. Y., Sklar, L. A., Koch, W. J., and Tesmer, J. J. (2012) Paroxetine is a direct inhibitor of G protein-coupled receptor kinase 2 and increases myocardial contractility. ACS Chem. Biol. 7, 1830-1839
26. Otwinoski, Z., and Minor, W. (1997) Processing of x-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326
27. Homan, K. T., Larimore, K. M., Elkins, J. M., Szklarz, M., Knapp, S., and Tesmer, J. J. (2015) Identification and structure-function analysis of subfamily selective G protein-coupled receptor kinase inhibitors. ACS Chem. Biol. 10, 310-319
28. Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G., McCoy, A., McNicholas, S. J., Murshudov, G. N., Pannu, N. S., Potterton, E. A., Powell, H. R., et al. (2011) Overview of the CCP4 suite and current developments. Acta Crystallogr. D. Biol. Crystallogr. 67, 235-242
29. Emsley, P., and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. D. Biol. Crystallogr. 60, 2126-2132
30. Chen, V. B., Arendall, W. B., 3rd, Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., and Richardson, D. C. (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D. Biol. Crystallogr. 66, 12-21
31. DeLano, W. (2002) The PyMOL Molecular Graphics System, Version 1.7.6.2 enhanced for Mac OS X, DeLano Scientific, San Carlos, CA
32. Papermaster, D. S. (1982) Preparation of antibodies to rhodopsin and the large protein of rod outer segments. Methods Enzymol. 81, 240-246
33. Gold, J. I., Gao, E., Shang, X., Premont, R. T., and Koch, W. J. (2012) Determining the absolute requirement of G protein-coupled receptor kinase 5 for pathological cardiac hypertrophy: short communication. Circ. Res. 111, 1048-1053
34. Dorn, G. W., 2nd. (2009) GRK mythology: G-protein receptor kinases in cardiovascular disease. J. Mol. Med. 87, 455-463
35. Tesmer, J. J., Tesmer, V. M., Lodowski, D. T., Steinhagen, H., and Huber, J. (2010) Structure of human G protein-coupled receptor kinase 2 in complex with the kinase inhibitor balanol. J. Med. Chem. 53, 1867-1870
36. Homan, K. T., and Tesmer, J. J. (2015) Molecular basis for small molecule inhibition of G protein-coupled receptor kinases. ACS Chem. Biol. 10, 246-256
37. Kannan, N., Haste, N., Taylor, S. S., and Neuwald, A. F. (2007) The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module. Proc. Natl. Acad. Sci. U.S.A. 104, 1272-1277
38. Narayana, N., Diller, T. C., Koide, K., Bunnage, M. E., Nicolaou, K. C., Brunton, L. L., Xuong, N. H., Ten Eyck, L. F., and Taylor, S. S. (1999) Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of cAMP-dependent protein kinase. Biochemistry 38, 2367-2376
39. Lodowski, D. T., Tesmer, V. M., Benovic, J. L., and Tesmer, J. J. (2006) The structure of G protein-coupled receptor kinase (GRK)-6 defines a second lineage of GRKs. J. Biol. Chem. 281, 16785-16793
40. Singh, P., Wang, B., Maeda, T., Palczewski, K., and Tesmer, J. J. (2008) Structures of rhodopsin kinase in different ligand states reveal key elements involved in G protein-coupled receptor kinase activation. J. Biol. Chem. 283, 14053-14062
41. Tesmer, J. J., Nance, M. R., Singh, P., and Lee, H. (2012) Structure of a monomeric variant of rhodopsin kinase at 2.5 A resolution. Acta Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 68, 622-625
42. Goodman, K. B., Cui, H., Dowdell, S. E., Gaitanopoulos, D. E., Ivy, R. L., Sehon, C. A., Stavenger, R. A., Wang, G. Z., Viet, A. Q., Xu, W., Ye, G., Semus, S. F., Evans, C., Fries, H. E., Jolivette, L. J., et al. (2007) Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors. J. Med. Chem. 50, 6-9
43. Pronin, A. N., and Benovic, J. L. (1997) Regulation of the G protein-coupled receptor kinase GRK5 by protein kinase C. J. Biol. Chem. 272, 3806-3812
44. Madhusudan, Akamine, P., Xuong, N. H., and Taylor, S. S. (2002) Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase. Nat. Struct. Biol. 9, 273-277
45. Gaffarogullari, E. C., Masterson, L. R., Metcalfe, E. E., Traaseth, N. J., Balatri, E., Musa, M. M., Mullen, D., Distefano, M. D., and Veglia, G. (2011) A myristoyl/phosphoserine switch controls cAMP-dependent protein kinase association to membranes. J. Mol. Biol. 411, 823-836
46. Ames, J. B., Lim, S., and Ikura, M. (2012) Molecular structure and target recognition of neuronal calcium sensor proteins. Front. Mol. Neurosci. 5, 10
47. Loudon, R. P., and Benovic, J. L. (1994) Expression, purification, and characterization of the G protein-coupled receptor kinase GRK6. J. Biol. Chem. 269, 22691-22697
48. 2-adrenergic receptor in plasma membranes by intrinsic GRK5. Biochemistry 46, 14438-14449
49. 2 binding site distinguishes the GRK subfamilies. J. Biol. Chem. 271, 24907-24913
50. Thal, D. M., Yeow, R. Y., Schoenau, C., Huber, J., and Tesmer, J. J. (2011) Molecular mechanism of selectivity among G protein-coupled receptor kinase 2 inhibitors. Mol. Pharmacol. 80, 294-303
51. Koide, K., Bunnage, M. E., Gomez Paloma, L., Kanter, J. R., Taylor, S. S., Brunton, L. L., and Nicolaou, K. C. (1995) Molecular design and biological activity of potent and selective protein kinase inhibitors related to balanol. Chem. Biol. 2, 601-608
52. Komolov, K. E., Bhardwaj, A., and Benovic, J. L. (2015) Atomic structure of G protein-coupled receptor kinase 5 (GRK5) reveals distinct structural features novel for GRKs. J. Biol. Chem. 290, 10.1074/jbc.M115.647297