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Title
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Three-dimensional structure of recombinant human muscle fatty acid-binding protein.
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Authors
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G.Zanotti,
G.Scapin,
P.Spadon,
J.H.Veerkamp,
J.C.Sacchettini.
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Ref.
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J Biol Chem, 1992,
267,
18541-18550.
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PubMed id
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Abstract
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The three-dimensional structure of recombinant human muscle fatty acid-binding
protein with a bound fatty acid has been solved and refined with x-ray
diffraction data to 2.1 A resolution. The refined model has a crystallographic R
factor of 19.5% for data between 9.0 and 2.1 A (7243 unique reflections) and
root-mean-square deviations in bond length and bond angle of 0.013 A and 2.7
degrees. The protein contains 10 antiparallel beta-strands and two short
alpha-helices which are arranged into two approximately orthogonal beta-sheets.
Difference electron density maps and a multiple isomorphous derivative electron
density map showed the presence of a single bound molecule of a long chain fatty
acid within the interior core of the protein. The hydrocarbon tail of the fatty
acid was found to be in a "U-shaped" conformation. Seven ordered water molecules
were also identified within the interior of the protein in a pocket on the
pseudo-si face of the fatty acid's bent hydrocarbon tail. The methylene tail of
the fatty acid forms van der Waals interactions with atoms from 13 residues and
three ordered waters. The carboxylate of the fatty acid is located in the
interior of the protein where it forms hydrogen bonds with the side chains of
Tyr128 and Arg126 and two ordered water molecules. A comparison of the
three-dimensional structure of human muscle fatty acid-binding protein and rat
intestinal fatty acid-binding protein shows strong similarity. Both proteins
bind a single fatty acid within their interior cores, but the bound fatty acids
are very different in their conformations and interactions. These findings
suggest that the intestinal and muscle fatty acid-binding proteins have evolved
distinct binding sites in order to satisfy different requirements within the
tissues where they are expressed.
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