Culminating Project Title
Date of Award
Culminating Project Type
Biological Sciences - Cell and Molecular: M.S.
College of Science and Engineering
Bruce L. Jacobson
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
The fatty acid-binding proteins (FABPs) are a family of nine structurally related proteins, which bind to long-chain fatty acids with high affinity. Fatty acid binding proteins were first discovered in 1972, while conducting studies on the factors that regulate the uptake of intestinal fatty acids in rats. These proteins are most abundantly found in the tissues engaged in active lipid metabolism. Adipocyte fatty acid binding protein or aP2 is a member of this family, which is found in adipocytes and macrophages and integrates metabolic and inflammatory responses (Furuhashi et al., 2007).
Studies on aP2 knockout mice have shown that aP2 null mice were more insulin sensitive compared to their wild type counterparts when kept on a high fat diet. This lipid chaperone plays an important role in metabolic syndromes, including type 2 diabetes and atherosclerosis. Targeting aP2 with small-molecule inhibitors can lead to a new class of therapeutic agents that may provide a model of study to prevent metabolic diseases such as type 2 diabetes.
This study focuses on the purification of aP2 by ion exchange chromatography in preparation for co-crystallization with ibuprofen. Previous attempts to do this have failed due to the tight binding of fatty acid at the binding site of the protein. To overcome this issue, delipidation was attempted by means of chromatography using the Lipidex 1000 sorbent. The purified protein was crystallized using the hanging drop method with seeding in the presence of ibuprofen. This study describes the crystal structure of human aP2 with bound ibuprofen at 1.4 Å resolution. Crystalline 3
aP2 was orthorhombic with cell dimensions of a = 32.20 Å, b = 53.64 Å, c = 74.44 Å and the space group was P212121.
Sharma, Anshu, "X-ray Crystallographic Structure of Ibuprofen Bound to Human Adipocyte Fatty Acid Binding Protein at 1.4 Å Resolution" (2016). Culminating Projects in Biology. 8.