1KZX

Solution structure of human intestinal fatty acid binding protein with a naturally-occurring single amino acid substitution (A54T)

1KZX の概要

• エントリーDOI: 10.2210/pdb1kzx/pdb
• 関連するPDBエントリー: 1KZW 3IFB
• NMR情報: BMRB: 5285
• 分子名称: INTESTINAL FATTY ACID-BINDING PROTEIN (T54) (1 entity in total)
• 機能のキーワード: nmr spectroscopy, 15n isotope labelling, fatty acid binding, type 2 diabetes, single base polymorphism, holo-form, lipid binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P12104
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15128.07

構造登録者

Zhang, F.,Luecke, C.,Baier, L.J.,Sacchettini, J.C.,Hamilton, J.A. (登録日: 2002-02-08, 公開日: 2003-07-01, 最終更新日: 2024-05-22)

主引用文献

Zhang, F.,Luecke, C.,Baier, L.J.,Sacchettini, J.C.,Hamilton, J.A.
Solution structure of human intestinal fatty acid binding protein with a naturally-occurring single amino acid substitution (A54T) that is associated with altered lipid metabolism
Biochemistry, 42:7339-7347, 2003

PubMed Abstract: The human intestinal fatty acid binding protein (I-FABP) belongs to a family of intracellular lipid binding proteins. This 15 kDa protein binds dietary long-chain fatty acids in the cytosol of enterocytes. A naturally-occurring nucleotide polymorphism at codon 54, which produces either an alanine-containing (A54) or a threonine-containing (T54) protein, has been identified. These two I-FABP forms display differential binding and transport of fatty acids across cells, and their alleles are associated with in vivo insulin resistance and/or altered lipid metabolism in several human populations. The three-dimensional solution structure of the more common A54 form was previously determined in our lab. A direct comparison between human A54 and T54 I-FABP has now been performed to help elucidate the structural origins of their physiological distinctions. The solution structure of T54 I-FABP is highly homologous to that of A54 I-FABP, with the same overall three-dimensional fold that includes an antiparallel beta-clam motif. Chemical shift differences between the two proteins suggest only minor local structural changes within the "portal region" and no significant alterations elsewhere. Hence, the slightly stronger binding of fatty acids to T54 I-FABP does not originate from residues in direct contact with the bound fatty acid. Instead, it appears that the larger Thr(54) side chain affects the passage of the ligand through the entry portal. Structural details of this portal region will be discussed in view of the influence residue 54 exerts on the functional properties of human I-FABP.

PubMed: 12809489
DOI: 10.1021/bi0273617

実験手法

SOLUTION NMR