1VYG

schistosoma mansoni fatty acid binding protein in complex with arachidonic acid

1VYG の概要

• エントリーDOI: 10.2210/pdb1vyg/pdb
• 関連するPDBエントリー: 1VYF
• 分子名称: FATTY ACID BINDING PROTEIN, ARACHIDONIC ACID (3 entities in total)
• 機能のキーワード: fatty acid binding protein, transport protein
• 由来する生物種: SCHISTOSOMA MANSONI (BLOOD FLUKE)
• 細胞内の位置: Cytoplasm (By similarity): P29498
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15315.38

構造登録者

Angelucci, F.,Johnson, K.A.,Baiocco, P.,Miele, A.E.,Bellelli, A. (登録日: 2004-04-29, 公開日: 2004-09-23, 最終更新日: 2023-12-13)

主引用文献

Angelucci, F.,Johnson, K.A.,Baiocco, P.,Miele, A.E.,Brunori, M.,Valle, C.,Vigorosi, F.,Troiani, A.R.,Liberti, P.,Cioli, D.,Klinkert, M.Q.,Bellelli, A.
Schistosoma Mansoni Fatty Acid Binding Protein: Specificity and Functional Control as Revealed by Crystallographic Structure
Biochemistry, 43:13000-, 2004

PubMed Abstract: Schistosoma mansoni fatty acid binding protein (Sm14) was crystallized with bound oleic acid (OLA) and arachidonic acid (ACD), and their structures were solved at 1.85 and 2.4 A resolution, respectively. Sm14 is a vaccine target for schistosomiasis, the second most prevalent parasitic disease in humans. The parasite is unable to synthesize fatty acids depending on the host for these nutrients. Moreover, arachidonic acid (ACD) is required to synthesize prostaglandins employed by schistosomes to evade the host's immune defenses. In the complex, the hydrocarbon tail of bound OLA assumes two conformations, whereas ACD adopts a unique hairpin-looped structure. ACD establishes more specific interactions with the protein, among which the most important is a pi-cation bond between Arg78 and the double bond at C8. Comparison with homologous fatty acid binding proteins suggests that the binding site of Sm14 is optimized to fit ACD. To test the functional implications of our structural data, the affinity of Sm14 for 1,8-anilinonaphthalenesulfonic acid (ANS) has been measured; moreover the binding constants of six different fatty acids were determined from their ability to displace ANS. OLA and ACD exhibited the highest affinities. To determine the rates of fatty acid binding and dissociation we carried out stopped flow kinetic experiments monitoring displacement by (and of) ANS. The binding rate constant of ligands is controlled by a slow pH dependent conformational change, which we propose to have physiological relevance.

PubMed: 15476393
DOI: 10.1021/BI048505F

実験手法

X-RAY DIFFRACTION (2.4 Å)