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PDBsum entry 1e7f
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Plasma protein
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PDB id
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1e7f
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystallographic analysis reveals common modes of binding of medium and long-Chain fatty acids to human serum albumin.
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Authors
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A.A.Bhattacharya,
T.Grüne,
S.Curry.
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Ref.
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J Mol Biol, 2000,
303,
721-732.
[DOI no: ]
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PubMed id
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Abstract
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Human serum albumin (HSA) is an abundant plasma protein that is responsible for
the transport of fatty acids. HSA also binds and perturbs the pharmacokinetics
of a wide range of drug compounds. Binding studies have revealed significant
interactions between fatty acid and drug-binding sites on albumin but
high-resolution structural information on ligand binding to the protein has been
lacking. We report here a crystallographic study of five HSA-fatty acid
complexes formed using saturated medium-chain and long-chain fatty acids (C10:0,
C12:0, C14:0, C16:0 and C18:0). A total of seven binding sites that are occupied
by all medium-chain and long-chain fatty acids have been identified, although
medium-chain fatty acids are found to bind at additional sites on the protein,
yielding a total of 11 distinct binding locations. Comparison of the different
complexes reveals key similarities and significant differences in the modes of
binding, and serves to rationalise much of the biochemical data on fatty acid
interactions with albumin. The two principal drug-binding sites, in sub-domains
IIA and IIIA, are observed to be occupied by fatty acids and one of them (in
IIIA) appears to coincide with a high-affinity long-chain fatty acid binding
site.
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Figure 1.
Figure 1. Structures of HSA complexed with five different
fatty acids. The protein secondary structure is shown
schematically and the domains are colour-coded as follows: I,
red; II, green, III, blue. The A and B sub-domains are depicted
in dark and light shades, respectively. This colour scheme is
maintained throughout. Bound fatty acids are shown in a
space-filling representation and coloured by atom type (carbon,
grey; oxygen, red). Where two fatty acid molecules bind in close
proximity, one of them is shown in a darker shade of grey. All
Figures were prepared using Bobscript [Esnouf 1997] and Raster3D
[Merrit and Bacon 1997].
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Figure 5.
Figure 5. Superposition of fatty acids bound to site 5 in
sub-domains IIIB. Amino acid side-chains for Y401 and K525 are
shown coloured by atom type.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2000,
303,
721-732)
copyright 2000.
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