Identification of the functional binding pocket for compounds targeting small-conductance Ca 2+ -activated potassium channels

Nature Communications

Volumn 3, Issue , 2012, Pages

  Zhang, Miao ^a   Pascal, John M ^b   Schumann, Marcel ^a   Armen, Roger S ^a   Zhang, Ji Fang ^a  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 ETHYL 2 BENZIMIDAZOLINONE; CALMODULIN; SMALL CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SELECTIVITY; INFORMATION PROCESSING; MOLECULAR DOCKING; MUTATION; NONHUMAN; PROTEIN ANALYSIS; PROTEIN STRUCTURE; PROTEIN TARGETING; RAT; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANIMALS; BENZIMIDAZOLES; BINDING SITES; CALCIUM; CALMODULIN; CRYSTALLOGRAPHY, X-RAY; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN STRUCTURE, TERTIARY; RATS; SEQUENCE ALIGNMENT; SMALL-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS;

EID: 84866074628     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms2017     Document Type: Article

References (60)

1. Kohler, M. et al. Small-conductance, calcium-activated potassium channels from mammalian brain. Science 273, 1709-1714 (1996). (Pubitemid 26317786)
2. Faber, E. S. L. & Sah, P. Functions of SK channels in central neurons. Clin. Exp. Pharmacol. Physiol. 34, 1077-1083 (2007). (Pubitemid 47274559)
3. Stocker, M. Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nat. Rev. Neurosci. 5, 758-770 (2004). (Pubitemid 39336213)
4. Xu, Y. et al. Molecular identification and functional roles of a Ca2+ activated K+ channel in human and mouse hearts. J. Biol. Chem. 278, 49085-49094 (2003).
5. Adelman, J. P., Maylie, J. & Sah, P. Small-conductance Ca2+-activated K+ channels: form and function. Annu. Rev. Physiol. 74, 245-269 (2012).
6. Xia, X. M. et al. Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature 395, 503-507 (1998).
7. Meador, W. E., Means, A. R. & Quiocho, F. A. Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex. Science 257, 1251-1255 (1992).
8. Schumacher, M. A., Rivard, A. F., Bachinger, H. P. & Adelman, J. P. Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin. Nature 410, 1120-1124 (2001). (Pubitemid 32391046)
9. Li, W., Halling, D. B., Hall, A. W. & Aldrich, R. W. EF hands at the N-lobe of calmodulin are required for both SK channel gating and stable SK-calmodulin interaction. J. Gen. Physiol. 134, 281-293 (2009).
10. Zhang, M. et al. Structural basis for calmodulin as a dynamic calcium sensor. Structure 20, 911-923 (2012).
11. Pedarzani, P. & Stocker, M. Molecular and cellular basis of small-and intermediate-conductance, calcium-activated potassium channel function in the brain. Cell. Mol. Life Sci. 65, 3196-3217 (2008).
12. Taylor, M. S. et al. Altered expression of small-conductance Ca2+-activated K+ (SK3) channels modulates arterial tone and blood pressure. Circ. Res. 93, 124-131 (2003). (Pubitemid 36919699)
13. Feng, J. et al. Calcium-activated potassium channels contribute to human coronary microvascular dysfunction after cardioplegic arrest. Circulation 118, S46-S51 (2008).
14. Garland, C. J. Compromised vascular endothelial cell SKCa activity: a fundamental aspect of hypertension? Br. J. Pharmacol. 160, 833-835 (2010).
15. Nagy, N. et al. Role of Ca2+-sensitive K+ currents in controlling ventricular repolarization: possible implications for future antiarrhytmic drug therapy. Curr. Med. Chem. 18, 3622-3639 (2011).
16. Marrelli, S. P., Eckmann, M. S. & Hunte, M. S. Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations. Am. J. Physiol. Heart Circ. Physiol. 285, H1590-H1599 (2003). (Pubitemid 37169514)
17. Si, H. et al. Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel. Circ. Res. 99, 537-544 (2006). (Pubitemid 44337826)
18. McNeish, A. J., Dora, K. A. & Garland, C. J. Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery. Stroke 36, 1526-1532 (2005). (Pubitemid 40967524)
19. Brahler, S. et al. Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation 119, 2323-2332 (2009).
20. Sheng, J.-Z., Ella, S., Davis, M. J., Hill, M. A. & Braun, A. P. Openers of SKCa and IKCa channels enhance agonist-evoked endothelial nitric oxide synthesis and arteriolar vasodilation. FASEB J. 23, 1138-1145 (2009).
21. Köhler, R. Single-nucleotide polymorphisms in vascular Ca2+-activated K+-channel genes and cardiovascular disease. Pflügers Arch. Eur. J. Physiol. 460, 343-351 (2010).
22. Allen, D. et al. SK2 channels are neuroprotective for ischemia-induced neuronal cell death. J. Cereb. Blood Flow Metab. 31, 2302-2312 (2011).
23. Chou, C. C., Lunn, C. A. & Murgolo, N. J. KCa3.1: target and marker for cancer, autoimmune disorder and vascular inflammation? Expert Rev. Mol. Diagn. 8, 179-187 (2008). (Pubitemid 351469437)
24. Chandy, K. G. et al. Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder? Mol. Psychiatry 3, 32-37 (1998). (Pubitemid 28045182)
25. Ritsner, M. et al. An association of CAG repeats at the KCNN3 locus with symptom dimensions of schizophrenia. Biol. Psychiatry 51, 788-794 (2002). (Pubitemid 34451065)
26. Ellinor, P. T. et al. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat. Genet. 42, 240-244 (2010).
27. Toyama, K. et al. The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans. J. Clin. Invest. 118, 3025-3037 (2008).
28. Girault, A. et al. Targeting SKCa channels in cancer: potential new therapeutic approaches. Curr. Med. Chem. 19, 697-713 (2011).
29. Blank, T., Nijholt, I., Kye, M.-J. & Spiess, J. Small conductance Ca2+-activated K+ channels as targets of CNS drug development. Curr. Drug Targets CNS Neurol. Disorders 3, 161-167 (2004). (Pubitemid 38854911)
30. Liegeois, J. et al. Modulation of small conductance calcium-activated potassium (SK) channels: a new challenge in medicinal chemistry. Curr. Med. Chem. 10, 625-647 (2003). (Pubitemid 36348085)
31. Wulff, H. & Zhorov, B. S. K+ channel modulators for the treatment of neurological disorders and autoimmune diseases. Chem. Rev. 108, 1744-1773 (2008). (Pubitemid 351796408)
32. Wulff, H. et al. Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant. Proc. Natl Acad. Sci. 97, 8151-8156 (2000). (Pubitemid 30460788)
33. Devor, D. C., Singh, A. K., Frizzell, R. A. & Bridges, R. J. Modulation of Cl-secretion by benzimidazolones. I. Direct activation of a Ca2+-dependent K+ channel. Am. J. Physiol. 271, L775-L784 (1996).
34. Anderson, N. J., Slough, S. & Watson, W. P. In vivo characterisation of the small-conductance KCa (SK) channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) as a potential anticonvulsant. Eur. J. Pharmacol. 546, 48-53 (2006). (Pubitemid 44331841)
35. Sankaranarayanan, A. et al. Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol. Pharmacol. 75, 281-295 (2009).
36. Hougaard, C. et al. Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels. Br. J. Pharmacol. 151, 655-665 (2007). (Pubitemid 47016300)
37. Pedarzani, P. et al. Control of electrical activity in central neurons by modulating the gating of small conductance Ca2+-activated K+ channels. J. Biol. Chem. 276, 9762-9769 (2001).
38. Taufer, M., Armen, R., Chen, J., Teller, P. & Brooks, C. Computational multiscale modeling in protein-ligand docking. IEEE Eng. Med. Biol. Mag. 28, 58-69 (2009).
39. Armen, R. S., Chen, J. & Brooks, C. L. 3rd. An evaluation of explicit receptor flexibility in molecular docking using molecular dynamics and torsion angle molecular dynamics. J. Chem. Theory Comput. 5, 2909-2923 (2009).
40. Cavasotto, C. N., Kovacs, J. A. & Abagyan, R. A. Representing receptor flexibility in ligand docking through relevant normal modes. J. Am. Chem. Soc. 127, 9632-9640 (2005). (Pubitemid 40934775)
41. Pedarzani, P. et al. Specific enhancement of SK channel activity selectively potentiates the after hyperpolarizing current IAHP and modulates the firing properties of hippocampal pyramidal neurons. J. Biol. Chem. 280, 41404-41411 (2005). (Pubitemid 41832199)
42. Scott, J. D & Pawson, T. Cell signaling in space and time: where proteins come together and when they're apart. Science 326, 1220-1224 (2009).
43. Gadek, T. R. & Nicholas, J. B. Cell signaling in space and time: where proteins come together and when they're apart. Science 326, 1220-1224 (2003).
44. Schön, A., Lam, S. Y. & Freire, E. Thermodynamics-based drug design: strategies for inhibiting protein-protein interactions. Future Med. Chem. 3, 1129-1137 (2011).
45. Fry, D. C. Protein-protein interactions as targets for small molecule drug discovery. Peptide Sci. 84, 535-552 (2006). (Pubitemid 44935254)
46. Arkin, M. R. & Whitty, A. The road less traveled: modulating signal transduction enzymes by inhibiting their protein-protein interactions. Curr. Opin. Chem. Biol. 13, 284-290 (2009).
47. Ataman, Z. A., Gakhar, L., Sorensen, B. R., Hell, J. W. & Shea, M. A. The NMDA receptor NR1 C1 region bound to calmodulin: structural insights into functional differences between homologous domains. Structure 15, 1603-1617 (2007). (Pubitemid 350213408)
48. Osawa, M. et al. A novel target recognition revealed by calmodulin in complex with Ca2+-calmodulin-dependent kinase kinase. Nat. Struct. Biol. 6, 819-824 (1999). (Pubitemid 29415172)
49. Chin, D. & Means, A. R. Calmodulin: a prototypical calcium sensor. Trends Cell Biol. 10, 322-328 (2000). (Pubitemid 30445239)
50. Clapham, D. E. Calcium signaling. Cell 131, 1047-1058 (2007). (Pubitemid 350258556)
51. Hoeflich, K. P. & Ikura, M. Calmodulin in action: diversity in target recognition and activation mechanisms. Cell 108, 739-742 (2002). (Pubitemid 34327526)
52. Winter, G. xia2: an expert system for macromolecular crystallography data reduction. J. Appl. Crystallogr. 43, 186-190 (2010).
53. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132 (2004). (Pubitemid 41742764)
54. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760-763 (1994).
55. Adams, P. D. et al. PHENIX: a comprehensive python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
56. Brooks, B. R. et al. Charmm -a program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 4, 187-217 (1983).
57. Roche, O., Kiyama, R. & Brooks, C. L. Ligand-Protein DataBase: linking protein-ligand complex structures to binding data. J. Med. Chem. 44, 3592-3598 (2001). (Pubitemid 33026666)
58. Vieth, M., Hirst, J. D., Kolinski, A. & Brooks, C. L. Assessing energy functions for flexible docking. J. Comput. Chem. 19, 1612-1622 (1998). (Pubitemid 128590220)
59. Rahaman, O. et al. Evaluation of several two-step scoring functions based on linear interaction energy, effective ligand size, and empirical pair potentials for prediction of protein-ligand binding geometry and free energy. J. Chem. Inf. Model 51, 2047-2065 (2011).
60. Armen, R. S., Schiller, S. M. & Brooks, C. L. 3rd. Steric and thermodynamic limits of design for the incorporation of large unnatural amino acids in aminoacyl-tRNA synthetase enzymes. Proteins 78, 1926-1938 (2010).