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Substitution of alanine for serine 250 in the murine fatty acid transport protein inhibits long chain fatty acid transport
Author(s): Stuhlsatz-Krouper SM, Bennett NE, Schaffer JE
Source: JOURNAL OF BIOLOGICAL CHEMISTRY    Volume: 273    Issue: 44    Pages: 28642-28650    Published: OCT 30 1998  
Times Cited: 48     References: 42     
Abstract: The murine fatty acid transport protein (FATP) was identified on the basis of its ability to facilitate uptake of long chain fatty acids (LCFAs) when expressed in mammalian cells. To delineate FATP domains important for transport function, we cloned the human heart FATP ortholog, Comparison of the human, murine, and yeast amino acid sequences identified a highly conserved motif, IYTSGTTGXPK, also found in a number of proteins that form adenylated intermediates. We demonstrate that depletion of intracellular ATP dramatically reduces FATP-mediated LCFA uptake. Furthermore, wildtype FATP specifically binds [alpha-P-32]azido-ATP. Introduction of a serine to alanine substitution (S250A) in the IYTSGTTGXPK motif produces an appropriately expressed and metabolized mutant FATP that demonstrates diminished LCFA transport function and decreased [alpha-P-32]azido-ATP binding. These results are consistent with a mechanism of action for FATP involving ATP binding that is dependent on serine 250 of the IYTSGTTGXPK motif.
Document Type: Article
Language: English
Reprint Address: Schaffer, JE (reprint author), Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Internal Med, 660 S Euclid Ave,Box 8086, St Louis, MO 63110 USA
Addresses:
1. Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Internal Med, St Louis, MO 63110 USA
2. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
Subject Category: Biochemistry & Molecular Biology
IDS Number: 133NC
ISSN: 0021-9258
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