Document Detail

Ala-504 is a determinant of substrate binding affinity in the mouse Na(+)/dicarboxylate cotransporter.
MedLine Citation:
PMID:  16787639     Owner:  NLM     Status:  MEDLINE    
The Na(+)/dicarboxylate cotransporters from mouse (mNaDC1) and rabbit (rbNaDC1) differ in their ability to handle adipate, a six-carbon terminal dicarboxylic acid. The mNaDC1 and rbNaDC1 amino acid sequences are 75% identical. The rbNaDC1 does not transport adipate and only succinate produced inward currents under two-electrode voltage clamp. In contrast, oocytes expressing mNaDC1 had adipate-dependent inward currents that were about 60% of those induced by succinate. In order to identify domains involved in adipate transport, we examined the functional properties of a series of chimeric transporters made between mouse and rabbit NaDC1. We find that multiple transmembrane helices (TM), particularly TM 8, 9, and 10, are involved in adipate transport. In TM 10 there is only one amino acid difference between the two proteins, corresponding to Ala-504 in mouse and Ser-512 in rabbit NaDC1. The mNaDC1-A504S mutant had decreased adipate-dependent currents relative to succinate-dependent currents and an increase in the K(0.5) for both succinate and glutarate. We conclude that multiple amino acids from TM 8, 9 and 10 contribute to the transport of adipate in NaDC1. Furthermore, Ala-504 in TM 10 is an important determinant of K(0.5) for both adipate and succinate.
Naomi Oshiro; Ana M Pajor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-05-16
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1758     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-07-25     Completed Date:  2006-09-20     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  781-8     Citation Subset:  IM    
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MeSH Terms
Alanine / chemistry,  metabolism*
Dicarboxylic Acid Transporters / genetics,  metabolism*
Mutagenesis, Site-Directed
Substrate Specificity
Grant Support
Reg. No./Substance:
0/Dicarboxylic Acid Transporters; OF5P57N2ZX/Alanine

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