Structural requirements of the human sodium-dependent bile acid transporter (hASBT): Role of 3- and 7-OH moieties on binding and translocation of bile acids

Molecular Pharmaceutics

Volumn 11, Issue 2, 2014, Pages 588-598

  González, Pablo M ^a   Lagos, Carlos F ^a   Ward, Weslyn C ^b   Polli, James E ^c  

^a PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE   (Chile)

^b Scynexis Inc   (United States)

^c UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY   (United States)

Author keywords

bile acid transporter; conformational analysis; inhibition; iso bile acids; permeability; translocation

Indexed keywords

APICAL SODIUM DEPENDENT BILE ACID TRANSPORTER; BILE ACID; CARRIER PROTEIN; GLYCINE; HYDROXYL GROUP; UNCLASSIFIED DRUG; COTRANSPORTER; ORGANIC ANION TRANSPORTER; PROTEIN BINDING; SODIUM-BILE ACID COTRANSPORTER;

ARTICLE; BILE ACID METABOLISM; BILE ACID SYNTHESIS; COMPUTER MODEL; CONFORMATION; EPIMER; HYDROXYLATION; ISOMER; ISOMERIZATION; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN STRUCTURE; ANTAGONISTS AND INHIBITORS; CHEMISTRY; HUMAN; METABOLISM; SYNTHESIS; TRANSPORT AT THE CELLULAR LEVEL;

BILE ACIDS AND SALTS; BIOLOGICAL TRANSPORT; HUMANS; HYDROXYLATION; MOLECULAR CONFORMATION; ORGANIC ANION TRANSPORTERS, SODIUM-DEPENDENT; PROTEIN BINDING; SYMPORTERS;

EID: 84893338555     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp400575t     Document Type: Article

References (48)

1. Sievanen, E. Exploitation of bile acid transport systems in prodrug design Molecules 2007, 12, 1859-89
2. Hofmann, A. F.; Hagey, L. R. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics Cell. Mol. Life Sci. 2008, 65, 2461-83
3. St-Pierre, M. V.; Kullak-Ublick, G. A.; Hagenbuch, B.; Meier, P. J. Transport of bile acids in hepatic and non-hepatic tissues J. Exp. Biol. 2001, 204, 1673-86 (Pubitemid 34865965)
4. Wong, M. H.; Oelkers, P.; Craddock, A. L.; Dawson, P. A. Expression cloning and characterization of the hamster ileal sodium-dependent bile acid transporter J. Biol. Chem. 1994, 269, 1340-7
5. Zhang, E. Y.; Phelps, M. A.; Banerjee, A.; Khantwal, C. M.; Chang, C.; Helsper, F.; Swaan, P. W. Topology scanning and putative three-dimensional structure of the extracellular binding domains of the apical sodium-dependent bile acid transporter (SLC10A2) Biochemistry 2004, 43, 11380-92 (Pubitemid 39186960)
6. Alrefai, W. A.; Gill, R. K. Bile acid transporters: structure, function, regulation and pathophysiological implications Pharm. Res. 2007, 24, 1803-23 (Pubitemid 47389235)
7. Cheng, J. B.; Jacquemin, E.; Gerhardt, M.; Nazer, H.; Cresteil, D.; Heubi, J. E.; Setchell, K. D.; Russell, D. W. Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease J. Clin. Endocrinol. Metab. 2003, 88, 1833-41 (Pubitemid 36623412)
8. Hamilton, J. P.; Xie, G.; Raufman, J. P.; Hogan, S.; Griffin, T. L.; Packard, C. A.; Chatfield, D. A.; Hagey, L. R.; Steinbach, J. H.; Hofmann, A. F. Human cecal bile acids: concentration and spectrum Am. J. Physiol. Gastrointest. Liver Physiol. 2007, 293, G256-63
9. Marschall, H. U.; Oppermann, U. C.; Svensson, S.; Nordling, E.; Persson, B.; Hoog, J. O.; Jornvall, H. Human liver class I alcohol dehydrogenase gammagamma isozyme: the sole cytosolic 3beta-hydroxysteroid dehydrogenase of iso bile acids Hepatology 2000, 31, 990-6 (Pubitemid 30169948)
10. Shefer, S.; Salen, G.; Hauser, S.; Dayal, B.; Batta, A. K. Metabolism of iso-bile acids in the rat J. Biol. Chem. 1982, 257, 1401-6 (Pubitemid 12121649)
11. Marschall, H. U.; Roeb, E.; Yildiz, Y.; Busch, N.; Nguyen, H.; Purucker, E.; Thomas, H. G.; Matern, S. Study of human isoursodeoxycholic acid metabolism J. Hepatol. 1997, 26, 863-70 (Pubitemid 27145711)
12. Marschall, H. U.; Broome, U.; Einarsson, C.; Alvelius, G.; Thomas, H. G.; Matern, S. Isoursodeoxycholic acid: metabolism and therapeutic effects in primary biliary cirrhosis J. Lipid Res. 2001, 42, 735-42 (Pubitemid 32507173)
13. Lack, L.; Weiner, I. M. Intestinal bile salt transport: structure-activity relationships and other properties Am. J. Physiol. 1966, 210, 1142-52
14. Baringhaus, K. H.; Matter, H.; Stengelin, S.; Kramer, W. Substrate specificity of the ileal and the hepatic Na(+)/bile acid cotransporters of the rabbit. II. A reliable 3D QSAR pharmacophore model for the ileal Na(+)/bile acid cotransporter J. Lipid Res. 1999, 40, 2158-68 (Pubitemid 30017517)
15. Fujino, T.; Une, M.; Imanaka, T.; Inoue, K.; Nishimaki-Mogami, T. Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation J. Lipid Res. 2004, 45, 132-8 (Pubitemid 38176623)
16. Wang, Y. D.; Chen, W. D.; Huang, W. FXR, a target for different diseases Histol. Histopathol. 2008, 23, 621-7 (Pubitemid 351552348)
17. Zollner, G.; Wagner, M.; Moustafa, T.; Fickert, P.; Silbert, D.; Gumhold, J.; Fuchsbichler, A.; Halilbasic, E.; Denk, H.; Marschall, H. U.; Trauner, M. Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-alpha/beta in the adaptive response to bile acids Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 290, G923-32
18. Zollner, G.; Fickert, P.; Fuchsbichler, A.; Silbert, D.; Wagner, M.; Arbeiter, S.; Gonzalez, F. J.; Marschall, H. U.; Zatloukal, K.; Denk, H.; Trauner, M. Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney and intestine J. Hepatol. 2003, 39, 480-8 (Pubitemid 37204645)
19. Pellicciari, R.; Costantino, G.; Fiorucci, S. Farnesoid X receptor: from structure to potential clinical applications J. Med. Chem. 2005, 48, 5383-403 (Pubitemid 41209235)
20. Katona, B. W.; Cummins, C. L.; Ferguson, A. D.; Li, T.; Schmidt, D. R.; Mangelsdorf, D. J.; Covey, D. F. Synthesis, characterization, and receptor interaction profiles of enantiomeric bile acids J. Med. Chem. 2007, 50, 6048-58
21. Balakrishnan, A.; Wring, S. A.; Polli, J. E. Interaction of native bile acids with human apical sodium-dependent bile acid transporter (hASBT): influence of steroidal hydroxylation pattern and C-24 conjugation Pharm. Res. 2006, 23, 1451-9 (Pubitemid 43993808)
22. Dayal, B.; Speck, J.; Bagan, E.; Tint, G. S.; Salen, G. p-Toluenesulfonic acid/methanol: mild reagent for the preparation of bile acid methyl esters Steroids 1981, 37, 239-42
23. Dias, J.; Ramachandra, R. Studies directed towards synthesis of quassinoids. III. Selective hydrolysis of the 3a-acetate functional group of cholic acid derivatives Synth. Commun. 1977, 7, 293-7
24. Batta, A. K.; Aggarwal, S. K.; Salen, G.; Shefer, S. Selective reduction of oxo bile acids: synthesis of 3 beta-, 7 beta-, and 12 beta-hydroxy bile acids J. Lipid Res. 1991, 32, 977-83
25. Chang, F. C. Potential bile acid metabolites. 2. 3,7,12-Trisubstituted 5.beta.-cholanic acids J. Org. Chem. 1979, 44, 4567-4572 (Pubitemid 10175042)
26. Balakrishnan, A.; Sussman, D. J.; Polli, J. E. Development of stably transfected monolayer overexpressing the human apical sodium-dependent bile acid transporter (hASBT) Pharm. Res. 2005, 22, 1269-80 (Pubitemid 41176030)
27. Balakrishnan, A.; Hussainzada, N.; Gonzalez, P.; Bermejo, M.; Swaan, P. W.; Polli, J. E. Bias in estimation of transporter kinetic parameters from overexpression systems: Interplay of transporter expression level and substrate affinity J. Pharmacol. Exp. Ther. 2007, 320, 133-44 (Pubitemid 46025728)
28. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
29. Zoete, V.; Cuendet, M. A.; Grosdidier, A.; Michielin, O. SwissParam: a fast force field generation tool for small organic molecules J. Comput. Chem. 2011, 32, 2359-68
30. Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics J. Mol. Graph. 1996, 14, 33-38 (Pubitemid 26152973)
31. Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, R. D.; Kale, L.; Schulten, K. Scalable molecular dynamics with NAMD J. Comput. Chem. 2005, 26, 1781-802 (Pubitemid 43078511)
32. MacKerell, A. D.; Bashford, D.; Bellott, M.; Dunbrack, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins J. Chem. Phys. B 1998, 102, 3586-3616 (Pubitemid 128576688)
33. Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A smooth particle mesh Ewald method J. Chem. Phys. 1995, 103, 8577-8593
34. Feller, S. E.; Zhang, Y.; Pastor, R. W.; Brooks, B. R. Constant pressure molecular dynamics simulation: The Langevin piston method J. Chem. Phys. 1995, 103, 4613-4621
35. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water J. Chem. Phys. 1983, 79, 926-935
36. Seeber, M.; Cecchini, M.; Rao, F.; Settanni, G.; Caflisch, A. Wordom: a program for efficient analysis of molecular dynamics simulations Bioinformatics 2007, 23, 2625-2627 (Pubitemid 350048368)
37. Gonzalez, P.; Polli, J. E. Impact of impurity on kinetic estimates from transport and inhibition studies J. Pharmacol. Exp. Ther. 2008, 326, 296-305 (Pubitemid 351872138)
38. Fini, A.; Roda, A. Chemical properties of bile acids. IV. Acidity constants of glycine-conjugated bile acids J. Lipid Res. 1987, 28, 755-9
39. Van Winkle, L. J. Biomembrane Transport, 1 st ed.; Academic Press: San Diego, 1999; p 397.
40. Posa, M.; Kuhajda, K. Hydrophobicity and haemolytic potential of oxo derivatives of cholic, deoxycholic and chenodeoxycholic acids Steroids 2010, 75, 424-31
41. Roda, A.; Hofmann, A. F.; Mysels, K. J. The influence of bile salt structure on self-association in aqueous solutions J. Biol. Chem. 1983, 258, 6362-70 (Pubitemid 13106811)
42. Small, D. M.; Penkett, S. A.; Chapman, D. Studies on simple and mixed bile salt micelles by nuclear magnetic resonance spectroscopy Biochim. Biophys. Acta 1969, 176, 178-89
43. Posa, M.; Kevresan, S.; Mikov, M.; Cirin-Novta, V.; Kuhajda, K. Critical micellar concentrations of keto derivatives of selected bile acids: thermodynamic functions of micelle formation Colloids Surf., B: Biointerfaces 2008, 64, 151-61
44. Kuhn, B.; Mohr, P.; Stahl, M. Intramolecular hydrogen bonding in medicinal chemistry. J. Med. Chem. 53, 2601-11.
45. Sato, H.; Macchiarulo, A.; Thomas, C.; Gioiello, A.; Une, M.; Hofmann, A. F.; Saladin, R.; Schoonjans, K.; Pellicciari, R.; Auwerx, J. Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies J. Med. Chem. 2008, 51, 1831-41 (Pubitemid 351438866)
46. Shea, H. C.; Head, D. D.; Setchell, K. D.; Russell, D. W. Analysis of HSD3B7 knockout mice reveals that a 3alpha-hydroxyl stereochemistry is required for bile acid function Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 11526-33 (Pubitemid 47175046)
47. Gonzalez, P. M.; Hussainzada, N.; Swaan, P. W.; Mackerell, A. D., Jr.; Polli, J. E. Putative irreversible inhibitors of the human sodium-dependent bile acid transporter (hASBT; SLC10A2) support the role of transmembrane domain 7 in substrate binding/translocation Pharm. Res. 2012, 29, 1821-31
48. Hussainzada, N.; Da Silva, T. C.; Zhang, E. Y.; Swaan, P. W. Conserved aspartic acid residues lining the extracellular loop 1 of sodium-coupled bile acid transporter ASBT Interact with Na+ and 7alpha-OH moieties on the ligand cholestane skeleton J. Biol. Chem. 2008, 283, 20653-63