3U3U

Crystal structure of the tablysin-15-leukotriene E4 complex

3U3U の概要

• エントリーDOI: 10.2210/pdb3u3u/pdb
• 関連するPDBエントリー: 3U3L 3U3N
• 分子名称: Tablysin 15, PRASEODYMIUM ION, CITRIC ACID, ... (5 entities in total)
• 機能のキーワード: cap domain, binding protein, integrin alphavbeta3 and leukotriene e4, protein binding
• 由来する生物種: Tabanus yao
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26922.24

構造登録者

Andersen, J.F. (登録日: 2011-10-06, 公開日: 2012-02-15, 最終更新日: 2024-10-16)

主引用文献

Xu, X.,Francischetti, I.M.,Lai, R.,Ribeiro, J.M.,Andersen, J.F.
Structure of protein having inhibitory disintegrin and leukotriene scavenging functions contained in single domain.
J.Biol.Chem., 287:10967-10976, 2012

PubMed Abstract: The antihemostatic/antiangiogenic protein tablysin-15 is a member of the CAP (cysteine-rich secretory, antigen 5, and pathogenesis-related 1 protein) superfamily and has been shown to bind the integrins α(IIb)β(3) and α(V)β(3) by means of an Arg-Gly-Asp (RGD) tripeptide sequence. Here we describe the x-ray crystal structure of tablysin-15 and show that the RGD motif is located in a novel structural context. The motif itself is contained in a type II β-turn structure that is similar in its conformation to the RGD sequence of the cyclic pentapeptide cilengitide when bound to integrin α(V)β(3). The CAP domain also contains a hydrophobic channel that appears to bind a fatty acid molecule in the crystal structure after purification from Escherichia coli. After delipidation of the protein, tablysin-15 was found to bind proinflammatory cysteinyl leukotrienes with submicromolar affinities. The structure of the leukotriene E(4)-tablysin-15 complex shows that the ligand binds with the nonfunctionalized end of the fatty acid chain buried in the hydrophobic pocket, whereas the carboxylate end of the ligand binds forms hydrogen bond/salt bridge interactions with polar side chains at the channel entrance. Therefore, tablysin-15 functions as an inhibitor of integrin function and as an anti-inflammatory scavenger of eicosanoids.

PubMed: 22311975
DOI: 10.1074/jbc.M112.340471

実験手法

X-RAY DIFFRACTION (2.5 Å)