你或許不知道，牛虻唾液腺中含有豐富的抗血栓活性物質(zhì),。近幾年來,，中國科學院昆明動物研究所賴仞研究員領導的學科組從牛虻唾液腺中識別了大量的抗血栓功能物質(zhì)。
近日,，該研究團隊在以前工作的基礎上與美國NIH John博士領導的團隊合作研究發(fā)現(xiàn),，牛虻唾液腺中的一個血小板聚集抑制因子含有一獨特的空間結(jié)構(gòu)域，該結(jié)構(gòu)域既是血小板膜受體aIIbb3的結(jié)合位點,，同時也結(jié)合類十二烷酸物質(zhì),。類十二烷酸包括血栓烷、白三烯,、前列腺環(huán)素和前列腺素等4大類物質(zhì),，具有導致血管收縮、發(fā)炎等生物功能,，是導致血栓,、血管硬化的重要因素。目前的研究結(jié)果表明,，該雙功能蛋白不僅可以通過抑制血小板功能,，同時也以通過清除類十二烷酸來達到抗血栓的目的。
可同時結(jié)合血小板膜受體和類十二烷酸的雙功能結(jié)構(gòu)域的識別為開發(fā)高效抗血栓藥物提供了先導模板,。相關(guān)論文發(fā)表在該研究成果已發(fā)表于國際學術(shù)期刊JBC上,。（生物谷Bioon.com）
doi:10.1074/jbc.M112.340471
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Structure of Protein Having Inhibitory Disintegrin and Leukotriene Scavenging Functions Contained in Single Domain
Xueqing Xu, Ivo M. B. Francischetti, Ren Lai§, José M. C. Ribeiro and John F. Andersen
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 αIIbβ3 and αVβ3 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 αVβ3. 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 E4-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.
