Molecular determinants of non-competitive antagonist binding to the mouse GPRC6A receptor

Cell Calcium

Volumn 46, Issue 5-6, 2009, Pages 323-332

  Faure, Helene ^a   Gorojankina, Tatiana ^a   Rice, Nadejda ^a   Dauban, Philippe ^b   Dodd, Robert H ^b   Bräuner Osborne, Hans ^c   Rognan, Didier ^a   Ruat, Martial ^a  

^a CNRS   (France)

^b INSTITUT DE CHIMIE DES SUBSTANCES NATURELLES   (France)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Allosteric modulators; Calcium; GPCR; Parathyroid

Indexed keywords

2 CHLORO 6 [3 [1,1 DIMETHYL 2 (2 NAPHTHYL)ETHYLAMINO] 2 HYDROXYPROPOXY]BENZONITRILE; ALANINE; CALCIMIMETIC AGENT; CALCIUM ANTAGONIST; CALCIUM SENSING RECEPTOR; CALHEX 231; CALINDOL; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR C6A; GLUTAMIC ACID; GLUTAMINE; INOSITOL PHOSPHATE; ORNITHINE; PHENYLALANINE; TRYPTOPHAN; UNCLASSIFIED DRUG;

ALLOSTERISM; ARTICLE; BINDING COMPETITION; BINDING SITE; CELL STRAIN HEK293; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG STRUCTURE; HUMAN; HUMAN CELL; HYDROGEN BOND; MODULATION; MOLECULAR DYNAMICS; MOUSE; MUTATIONAL ANALYSIS; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN LOCALIZATION; SITE DIRECTED MUTAGENESIS; TRANSIENT EXPRESSION;

EID: 70849106449     PISSN: 01434160     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceca.2009.09.004     Document Type: Article

References (45)

1. Raddatz R., Schaffhauser H., and Marino M.J. Allosteric approaches to the targeting of G-protein-coupled receptors for novel drug discovery: a critical assessment. Biochem. Pharmacol. 74 (2007) 383-391
2. Lagerstrom M.C., and Schioth H.B. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat. Rev. Drug Discov. 7 (2008) 339-357
3. Brauner-Osborne H., Wellendorph P., and Jensen A.A. Structure, pharmacology and therapeutic prospects of family C G-protein coupled receptors. Curr. Drug Targets 8 (2007) 169-184
4. Brown E.M. The calcium-sensing receptor: physiology, pathophysiology and CaR-based therapeutics. Subcell. Biochem. 45 (2007) 139-167
5. Trivedi R., Mithal A., and Chattopadhyay N. Recent updates on the calcium-sensing receptor as a drug target. Curr. Med. Chem. 15 (2008) 178-186
6. Gowen M., Stroup G.B., Dodds R.A., et al. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J. Clin. Invest. 105 (2000) 1595-1604
7. 2+ binding pocket within the venus flytrap module of the human calcium-sensing receptor. J. Biol. Chem. 280 (2005) 37917-37923
8. Miedlich S.U., Gama L., Seuwen K., Wolf R.M., and Breitwieser G.E. Homology modeling of the transmembrane domain of the human calcium sensing receptor and localization of an allosteric binding site. J. Biol. Chem. 279 (2004) 7254-7263
9. 2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J. Biol. Chem. 279 (2004) 18990-18997
10. Petrel C., Kessler A., Maslah F., et al. Modeling and mutagenesis of the binding site of Calhex 231, a novel negative allosteric modulator of the extracellular Ca(2+)-sensing receptor. J. Biol. Chem. 278 (2003) 49487-49494
11. Pi M., Faber P., Ekema G., et al. Identification of a novel extracellular cation-sensing G-protein-coupled receptor. J. Biol. Chem. 280 (2005) 40201-40209
12. Ferry S., Traiffort E., Stinnakre J., and Ruat M. Developmental and adult expression of rat calcium-sensing receptor transcripts in neurons and oligodendrocytes. Eur. J. Neurosci. 12 (2000) 872-884
13. Christiansen B., Hansen K.B., Wellendorph P., and Brauner-Osborne H. Pharmacological characterization of mouse GPRC6A, an l-alpha-amino-acid receptor modulated by divalent cations. Br. J. Pharmacol. 150 (2007) 798-807
14. Kuang D., Yao Y., Lam J., Tsushima R.G., and Hampson D.R. Cloning and characterization of a family C orphan G-protein coupled receptor. J. Neurochem. 93 (2005) 383-391
15. Wellendorph P., Hansen K.B., Balsgaard A., et al. Deorphanization of GPRC6A: a promiscuous l-alpha-amino acid receptor with preference for basic amino acids. Mol. Pharmacol. 67 (2005) 589-597
16. Harno E., Edwards G., Geraghty A.R., et al. Evidence for the presence of GPRC6A receptors in rat mesenteric arteries. Cell Calcium 44 (2008) 210-219
17. Pi M., Chen L., Huang M.Z., et al. GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS ONE 3 (2008) e3858
18. Wellendorph P., Johansen L.D., Jensen A.A., et al. No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions. J. Mol. Endocrinol. 42 (2009) 215-223
19. Masdeu C., Faure H., Coulombe J., et al. Identification and characterization of Hedgehog modulator properties after functional coupling of Smoothened to G15. Biochem. Biophys. Res. Commun. 349 (2006) 471-479
20. D'Souza-Li L., Yang B., Canaff L., et al. Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia. J. Clin. Endocrinol. Metab. 87 (2002) 1309-1318
21. Heydorn A., Ward R.J., Jorgensen R., et al. Identification of a novel site within G protein alpha subunits important for specificity of receptor-G protein interaction. Mol. Pharmacol. 66 (2004) 250-259
22. 2+-sensing receptor. J. Biol. Chem. 271 (1996) 5972-5975
23. Coulombe J., Traiffort E., Loulier K., Faure H., and Ruat M. Hedgehog interacting protein in the mature brain: membrane-associated and soluble forms. Mol. Cell. Neurosci. 25 (2004) 323-333
24. Ballesteros J., and Weinstein H. Integrated methods for the construction of three-dimensional models and computational probing pf structure-function relations of G protein-coupled receptors. Methods Neurosci. 25 (1995) 366-428
25. Wu C.H., Apweiler R., Bairoch A., et al. The Universal Protein Resource (UniProt): an expanding universe of protein information. Nucleic Acids Res. 34 (2006) D187-D191
26. Larkin M.A., Blackshields G., Brown N.P., et al. Clustal W and Clustal X version 2.0. Bioinformatics 23 (2007) 2947-2948
27. Wang J., Wolf R.M., Caldwell J.W., Kollman P.A., and Case D.A. Development and testing of a general amber force field. J. Comput. Chem. 25 (2004) 1157-1174
28. Surgand J.S., Rodrigo J., Kellenberger E., and Rognan D. A chemogenomic analysis of the transmembrane binding cavity of human G-protein-coupled receptors. Proteins 62 (2006) 509-538
29. Marcou G., and Rognan D. Optimizing fragment and scaffold docking by use of molecular interaction fingerprints. J. Chem. Inf. Model. 47 (2007) 195-207
30. Kessler A., Faure H., Petrel C., et al. N1-benzoyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-diaminocyclohexanes: development of 4-chlorophenylcarboxamide (calhex 231) as a new calcium sensing receptor ligand demonstrating potent calcilytic activity. J. Med. Chem. 49 (2006) 5119-5128
31. Kessler A., Faure H., Petrel C., et al. N2-benzyl-N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and conformationally restrained indole analogues: development of calindol as a new calcimimetic acting at the calcium sensing receptor. Bioorg. Med. Chem. Lett. 14 (2004) 3345-3349
32. Wellendorph P., Burhenne N., Christiansen B., et al. The rat GPRC6A: cloning and characterization. Gene 396 (2007) 257-267
33. de Graaf C., Foata N., Engkvist O., and Rognan D. Molecular modeling of the second extracellular loop of G-protein coupled receptors and its implication on structure-based virtual screening. Proteins 71 (2008) 599-620
34. Wellendorph P., and Brauner-Osborne H. Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor. Gene 335 (2004) 37-46
35. 2+ and a positive allosteric modulator. J. Biol. Chem. 277 (2002) 46622-46631
36. Hu J., and Spiegel A.M. Structure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators. J. Cell. Mol. Med. 11 (2007) 908-922
37. Brauner-Osborne H., Jensen A.A., Sheppard P.O., O'Hara P., and Krogsgaard-Larsen P. The agonist-binding domain of the calcium-sensing receptor is located at the amino-terminal domain. J. Biol. Chem. 274 (1999) 18382-18386
38. Huang Y., Zhou Y., Yang W., et al. Identification and dissection of Ca(2+)-binding sites in the extracellular domain of Ca(2+)-sensing receptor. J. Biol. Chem. 282 (2007) 19000-19010
39. 2+ receptor converts a negative allosteric modulator into a positive allosteric modulator. J. Biol. Chem. 281 (2006) 21558-21565
40. Muhlemann A., Ward N.A., Kratochwil N., et al. Determination of key amino acids implicated in the actions of allosteric modulation by 3,3′-difluorobenzaldazine on rat mGlu5 receptors. Eur. J. Pharmacol. 529 (2006) 95-104
41. O'Brien J.A., Lemaire W., Chen T.B., et al. A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5. Mol. Pharmacol. 64 (2003) 731-740
42. Brown E.M., Gamba G., Riccardi D., et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 366 (1993) 575-580
43. Ruat M., Molliver M.E., Snowman A.M., and Snyder S.H. Calcium sensing receptor: molecular cloning in rat and localization to nerve terminals. Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 3161-3165
44. Kunishima N., Shimada Y., Tsuji Y., et al. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407 (2000) 971-977
45. Schwalbe H., and Wess G. Dissecting G-protein-coupled receptors: structure, function, and ligand interaction. Chembiochem 3 (2002) 915-919