PI Global Investments
Precious Metals

Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole


  • Yelshanskaya, M. V., Nadezhdin, K. D., Kurnikova, M. G. & Sobolevsky, A. I. Structure and function of the calcium-selective TRP channel TRPV6. J. Physiol. 599, 2673–2697 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hoenderop, J. G. et al. Function and expression of the epithelial Ca2+ channel family: comparison of mammalian ECaC1 and 2. J. Physiol. 537, 747–761 (2001).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vennekens, R., Voets, T., Bindels, R. J., Droogmans, G. & Nilius, B. Current understanding of mammalian TRP homologues. Cell Calcium 31, 253–264 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • den Dekker, E., Hoenderop, J. G., Nilius, B. & Bindels, R. J. The epithelial calcium channels, TRPV5 & TRPV6: from identification towards regulation. Cell Calcium 33, 497–507 (2003).

    Article 
    CAS 

    Google Scholar
     

  • Fecher-Trost, C., Weissgerber, P. & Wissenbach, U. TRPV6 channels. Handb. Exp. Pharm. 222, 359–384 (2014).

    Article 
    CAS 

    Google Scholar
     

  • Zakharian, E., Cao, C. & Rohacs, T. Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5)P2. FASEB J. 25, 3915–3928 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cai, R. et al. Autoinhibition of TRPV6 channel and regulation by PIP2. iScience 23, 101444 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Thyagarajan, B., Lukacs, V. & Rohacs, T. Hydrolysis of phosphatidylinositol 4,5-bisphosphate mediates calcium-induced inactivation of TRPV6 channels. J. Biol. Chem. 283, 14980–14987 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Voets, T., Janssens, A., Prenen, J., Droogmans, G. & Nilius, B. Mg2+-dependent gating and strong inward rectification of the cation channel TRPV6. J. Gen. Physiol. 121, 245–260 (2003).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Owsianik, G., Talavera, K., Voets, T. & Nilius, B. Permeation and selectivity of TRP channels. Annu. Rev. Physiol. 68, 685–717 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lambers, T. T., Weidema, A. F., Nilius, B., Hoenderop, J. G. & Bindels, R. J. Regulation of the mouse epithelial Ca2+ channel TRPV6 by the Ca2+-sensor calmodulin. J. Biol. Chem. 279, 28855–28861 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Derler, I. et al. Dynamic but not constitutive association of calmodulin with rat TRPV6 channels enables fine tuning of Ca2+-dependent inactivation. J. Physiol. 577, 31–44 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nilius, B. et al. Fast and slow inactivation kinetics of the Ca2+ channels ECaC1 and ECaC2 (TRPV5 and TRPV6). Role of the intracellular loop located between transmembrane segments 2 and 3. J. Biol. Chem. 277, 30852–30858 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Singh, A. K., McGoldrick, L. L., Twomey, E. C. & Sobolevsky, A. I. Mechanism of calmodulin inactivation of the calcium-selective TRP channel TRPV6. Sci. Adv. 4, eaau6088 (2018).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bianco, S. D. et al. Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. J. Bone Miner. Res. 22, 274–285 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Suzuki, Y. et al. Calcium channel TRPV6 is involved in murine maternal-fetal calcium transport. J. Bone Miner. Res 23, 1249–1256 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weissgerber, P. et al. Male fertility depends on Ca2+ absorption by TRPV6 in epididymal epithelia. Sci. Signal. 4, ra27 (2011).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Weissgerber, P. et al. Excision of Trpv6 gene leads to severe defects in epididymal Ca2+ absorption and male fertility much like single D541A pore mutation. J. Biol. Chem. 287, 17930–17941 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lieben, L. et al. Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis. Bone 47, 301–308 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wangemann, P. et al. Loss of cochlear HCO3– secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model. Am. J. Physiol. Ren. Physiol. 292, F1345–F1353 (2007).

    Article 
    CAS 

    Google Scholar
     

  • Huybers, S. et al. Murine TNF(DeltaARE) Crohn’s disease model displays diminished expression of intestinal Ca2+ transporters. Inflamm. Bowel Dis. 14, 803–811 (2008).

    Article 
    PubMed 

    Google Scholar
     

  • Wu, G. et al. Suppression of intestinal calcium entry channel TRPV6 by OCRL, a lipid phosphatase associated with Lowe syndrome and Dent disease. Am. J. Physiol. Cell Physiol. 302, C1479–C1491 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, S. S. et al. Generation and analysis of the thiazide-sensitive Na+-Cl– cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome. Hum. Mutat. 31, 1304–1315 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Frick, K. K. et al. Increased biological response to 1,25(OH)2D3 in genetic hypercalciuric stone-forming rats. Am. J. Physiol. Ren. Physiol. 304, F718–F726 (2013).

    Article 
    CAS 

    Google Scholar
     

  • Hache, S. et al. Alteration of calcium homeostasis in primary preeclamptic syncytiotrophoblasts: effect on calcium exchange in placenta. J. Cell Mol. Med. 15, 654–667 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Suzuki, Y. et al. TRPV6 variants interfere with maternal-fetal calcium transport through the placenta and cause transient neonatal hyperparathyroidism. Am. J. Hum. Genet 102, 1104–1114 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Burren, C. P. et al. TRPV6 compound heterozygous variants result in impaired placental calcium transport and severe undermineralization and dysplasia of the fetal skeleton. Am. J. Med. Genet. A 176, 1950–1955 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nett, V., Erhardt, N., Wyatt, A. & Wissenbach, U. Human TRPV6-pathies caused by gene mutations. Biochim. Biophys. Acta Gen. Subj. 1865, 129873 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Masamune, A. et al. Variants that affect function of calcium channel TRPV6 are associated with early-onset chronic pancreatitis. Gastroenterology 158, 1626–1641 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Suzuki, Y. et al. Novel TRPV6 mutations in the spectrum of transient neonatal hyperparathyroidism. J. Physiol. Sci. 70, 33 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yamashita, S., Mizumoto, H., Sawada, H., Suzuki, Y. & Hata, D. TRPV6 gene mutation in a dizygous twin with transient neonatal hyperparathyroidism. J. Endocr. Soc. 3, 602–606 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zou, W. B. et al. TRPV6 variants confer susceptibility to chronic pancreatitis in the Chinese population. Hum. Mutat. 41, 1351–1357 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Stewart, J. M. TRPV6 as a target for cancer therapy. J. Cancer 11, 374–387 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huber, S. M. Oncochannels. Cell Calcium 53, 241–255 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Peng, J. B., Suzuki, Y., Gyimesi, G. & Hediger, M. A. in Calcium Entry Channels in Non-Excitable Cells (eds J. A. Kozak & J. W. Putney, Jr.) 241–274 (2018).

  • Schwarz, E. C. et al. TRPV6 potentiates calcium-dependent cell proliferation. Cell Calcium 39, 163–173 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lehen’kyi, V., Flourakis, M., Skryma, R. & Prevarskaya, N. TRPV6 channel controls prostate cancer cell proliferation via Ca2+/NFAT-dependent pathways. Oncogene 26, 7380–7385 (2007).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Bolanz, K. A., Hediger, M. A. & Landowski, C. P. The role of TRPV6 in breast carcinogenesis. Mol. Cancer Ther. 7, 271–279 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bowen, C. V. et al. In vivo detection of human TRPV6-rich tumors with anti-cancer peptides derived from soricidin. PLoS ONE 8, e58866 (2013).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Haverstick, D. M., Heady, T. N., Macdonald, T. L. & Gray, L. S. Inhibition of human prostate cancer proliferation in vitro and in a mouse model by a compound synthesized to block Ca2+ entry. Cancer Res. 60, 1002–1008 (2000).

    CAS 
    PubMed 

    Google Scholar
     

  • Landowski, C. P., Bolanz, K. A., Suzuki, Y. & Hediger, M. A. Chemical inhibitors of the calcium entry channel TRPV6. Pharm. Res. 28, 322–330 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kovacs, G. et al. Inhibition of the human epithelial calcium channel TRPV6 by 2-aminoethoxydiphenyl borate (2-APB). Cell Calcium 52, 468–480 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hofer, A. et al. Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport. Bioorg. Med. Chem. 21, 3202–3213 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Simonin, C. et al. Optimization of TRPV6 calcium channel inhibitors using a 3D ligand-based virtual screening method. Angew. Chem. 54, 14748–14752 (2015).

    Article 
    CAS 

    Google Scholar
     

  • Cunha, M. R. et al. Photoswitchable inhibitor of the calcium channel TRPV6. ACS Medicinal Chem. Lett. 10, 1341–1345 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Cunha, M. R. et al. Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor. RSC Med. Chem. 11, 1032–1040 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nilius, B. et al. Pharmacological modulation of monovalent cation currents through the epithelial Ca2+ channel ECaC1. Br. J. Pharm. 134, 453–462 (2001).

    Article 
    CAS 

    Google Scholar
     

  • Singh, A. K., Saotome, K., McGoldrick, L. L. & Sobolevsky, A. I. Structural bases of TRP channel TRPV6 allosteric modulation by 2-APB. Nat. Commun. 9, 2465 (2018).

    Article 
    ADS 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Bhardwaj, R. et al. Inactivation-mimicking block of the epithelial calcium channel TRPV6. Sci. Adv. 6, abe1508 (2020).

    Article 
    ADS 
    CAS 

    Google Scholar
     

  • Clarke, M. J. Ruthenium metallopharmaceuticals. Coord. Chem. Rev. 232, 69–93 (2002).

    Article 
    CAS 

    Google Scholar
     

  • Tapia, R. & Velasco, I. Ruthenium red as a tool to study calcium channels, neuronal death and the function of neural pathways. Neurochem. Int. 30, 137–147 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yamada, K. Dual staining of some sulfated mucopolysaccharides with alcian blue (pH 1.0) and ruthenium red (pH 2.5). Histochemie 23, 13–20 (1970).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pope, L., Lolicato, M. & Minor, D. L. Jr. Polynuclear ruthenium amines inhibit K2P channels via a “Finger in the Dam” mechanism. Cell Chem. Biol. 27, 511–524 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Choi, W., Clemente, N., Sun, W., Du, J. & Lu, W. The structures and gating mechanism of human calcium homeostasis modulator 2. Nature 576, 163–167 (2019).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McGoldrick, L. L. et al. Opening of the human epithelial calcium channel TRPV6. Nature 553, 233–237 (2018).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Saotome, K., Singh, A. K., Yelshanskaya, M. V. & Sobolevsky, A. I. Crystal structure of the epithelial calcium channel TRPV6. Nature 534, 506–511 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Singh, A. K., Saotome, K. & Sobolevsky, A. I. Swapping of transmembrane domains in the epithelial calcium channel TRPV6. Sci. Rep. 7, 10669 (2017).

    Article 
    ADS 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Long, S. B., Campbell, E. B. & Mackinnon, R. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309, 897–903 (2005).

    Article 
    ADS 
    CAS 

    Google Scholar
     

  • Sakipov, S., Sobolevsky, A. I. & Kurnikova, M. G. Ion permeation mechanism in epithelial calcium channel TRVP6. Sci. Rep. 8, 5715 (2018).

    Article 
    ADS 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Cao, E., Liao, M., Cheng, Y. & Julius, D. TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504, 113–118 (2013).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zubcevic, L., Le, S., Yang, H. & Lee, S. Y. Conformational plasticity in the selectivity filter of the TRPV2 ion channel. Nat. Struct. Mol. Biol. 25, 405–415 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hughes, T. E. T. et al. Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM. Nat. Struct. Mol. Biol. 25, 53–60 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gao, Y., Cao, E., Julius, D. & Cheng, Y. TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature 534, 347–351 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nadezhdin, K. D. et al. Extracellular cap domain is an essential component of the TRPV1 gating mechanism. Nat. Commun. 12, 2154 (2021).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Conde, J. et al. Allosteric antagonist modulation of TRPV2 by piperlongumine impairs glioblastoma progression. ACS Cent. Sci. 7, 868–881 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van Goor, M. K. C., Hoenderop, J. G. J. & van der Wijst, J. TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6. Biochim Biophys. Acta Mol. Cell Res. 1864, 883–893 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Na, T. & Peng, J. B. TRPV5: a Ca2+ channel for the fine-tuning of Ca2+ reabsorption. Handb. Exp. Pharm. 222, 321–357 (2014).

    Article 
    CAS 

    Google Scholar
     

  • Goehring, A. et al. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies. Nat. Protoc. 9, 2574–2585 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nasr, M. L. et al. Covalently circularized nanodiscs for studying membrane proteins and viral entry. Nat. Methods 14, 49–52 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Suloway, C. et al. Automated molecular microscopy: the new Leginon system. J. Struct. Biol. 151, 41–60 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput Chem. 25, 1605–1612 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D. Biol. Crystallogr. 66, 486–501 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D. 68, 352–367 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • The PyMOL Molecular Graphics System (DeLano Scientific, San Carlos, CA, USA, 2002).

  • Smart, O. S., Neduvelil, J. G., Wang, X., Wallace, B. A. & Samsom, M. S. HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J. Mol. Graph. 14, 354–360 (1996).

    Article 
    CAS 

    Google Scholar
     



  • Source link

    Related posts

    Centre tightens silver import rules, shifts key categories to ‘restricted’ list

    D.William

    South African supply constraints keep global PGM market tight

    D.William

    COAST CAPITAL ACQUIRES ADDITIONAL COMMON SHARES OF ARIZONA METALS CORP.

    D.William

    Leave a Comment