1fe3

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1fe3, resolution 2.8Å

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CRYSTAL STRUCTURE OF HUMAN BRAIN FATTY ACID BINDING PROTEIN OLEIC ACID

Contents

Overview

Expression of brain fatty acid-binding protein (B-FABP) is spatially and, temporally correlated with neuronal differentiation during brain, development. Isothermal titration calorimetry demonstrates that, recombinant human B-FABP clearly exhibits high affinity for the, polyunsaturated n-3 fatty acids alpha-linolenic acid, eicosapentaenoic, acid, docosahexaenoic acid, and for monounsaturated n-9 oleic acid (K(d), from 28 to 53 nm) over polyunsaturated n-6 fatty acids, linoleic acid, and, arachidonic acid (K(d) from 115 to 206 nm). B-FABP has low binding, affinity for saturated long chain fatty acids. The three-dimensional, structure of recombinant human B-FABP in complex with oleic acid shows, that the oleic acid hydrocarbon tail assumes a "U-shaped" conformation, whereas in the complex with docosahexaenoic acid the hydrocarbon tail, adopts a helical conformation. A comparison of the three-dimensional, structures and binding properties of human B-FABP with other homologous, FABPs, indicates that the binding specificity is in part the result of, nonconserved amino acid Phe(104), which interacts with double bonds, present in the lipid hydrocarbon tail. In this context, analysis of the, primary and tertiary structures of human B-FABP provides a rationale for, its high affinity and specificity for polyunsaturated fatty acids. The, expression of B-FABP in glial cells and its high affinity for, docosahexaenoic acid, which is known to be an important component of, neuronal membranes, points toward a role for B-FABP in supplying brain, abundant fatty acids to the developing neuron.

Disease

Known diseases associated with this structure: Infundibular hypoplasia and hypopituitarism OMIM:[313430], Mental retardation, X-linked, with isolated growth hormone deficiency OMIM:[313430]

About this Structure

1FE3 is a Single protein structure of sequence from Homo sapiens with OLA as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure and thermodynamic analysis of human brain fatty acid-binding protein., Balendiran GK, Schnutgen F, Scapin G, Borchers T, Xhong N, Lim K, Godbout R, Spener F, Sacchettini JC, J Biol Chem. 2000 Sep 1;275(35):27045-54. PMID:10854433

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