Document Detail

Identification of functionally relevant residues of the rat ileal apical sodium-dependent bile acid cotransporter.
MedLine Citation:
PMID:  16608845     Owner:  NLM     Status:  MEDLINE    
The mechanisms underlying the transport of bile acids by apical sodium-dependent bile acid transporter (Asbt) are not well defined. To further identify the functionally relevant residues, thirteen conserved negatively (Asp and Glu) and positively (Lys and Arg) charged residues plus Cys-270 of rat Asbt were replaced with Ala or Gln by site-directed mutagenesis. Seven of the fourteen residues of rat Asbt were identified as functionally important by taurocholate transport studies, substrate inhibition assays, confocal microscopy, and electrophysiological methods. The results showed that Asp-122, Lys-191, Lys-225, Lys-256, Glu-261, and Lys-312,Lys-313 residues of rat Asbt are critical for transport function and may determine substrate specificity. Arg-64 may be located at a different binding site to assist in interaction with non-bile acid organic anions. For bile acid transport by Asbt, Na(+) ion movement is a voltage-dependent process that tightly companied with taurocholate movement. Asp-122 and Glu-261 play a critical role in the interaction of a Na(+) ion and ligand with Asbt. Cys-270 is not essential for the transport process. These studies provide new details about the amino acid residues of Asbt involved in binding and transport of bile acids and Na(+).
An-Qiang Sun; Natarajan Balasubramaniyan; Haijun Chen; Mohammad Shahid; Frederick J Suchy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-04-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-12     Completed Date:  2006-08-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16410-8     Citation Subset:  IM    
Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
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MeSH Terms
Bile Acids and Salts / metabolism*
COS Cells
Carrier Proteins / metabolism,  physiology*
Cercopithecus aethiops
Ileum / pathology
Membrane Glycoproteins / metabolism,  physiology*
Mutagenesis, Site-Directed
Oocytes / metabolism
Sodium / metabolism
Taurocholic Acid / pharmacology
Xenopus laevis
Grant Support
1S10 RR 09145-01/RR/NCRR NIH HHS; 5R24 CA 095823-04/CA/NCI NIH HHS; 5R37 HD 020632-21/HD/NICHD NIH HHS
Reg. No./Substance:
0/Bile Acids and Salts; 0/Carrier Proteins; 0/Membrane Glycoproteins; 0/bile acid binding proteins; 7440-23-5/Sodium; 81-24-3/Taurocholic Acid

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