Structure of Protein Having Inhibitory Disintegrin and Leukotriene Scavenging Functions Contained in Single Domain
文献类型：期刊论文
| 作者 | Xu XQ1; Francischetti IMB1; Lai R[*]2; Ribeiro JMC1; Andersen JF[*]1 |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2012 |
| 卷号 | 287期号:14页码:10967-10976 |
| 通讯作者 | lairen72@yahoo.com.cn ; jandersen@niaid.nih.gov |
| 合作状况 | 其它 |
| 英文摘要 | 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 alpha(IIb)beta(3) and alpha(V)beta(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 beta-turn structure that is similar in its conformation to the RGD sequence of the cyclic pentapeptide cilengitide when bound to integrin alpha V beta 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 sub-micromolar 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. |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000302780100025 |
| 公开日期 | 2012-05-10 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6946]  |
| 专题 | 昆明动物研究所_动物毒素室 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Laboratory of Malaria and Vector Research,NIAID,National Intitutes of Health, Bethesda,Maryland 20892 2.Key Laboratory of Animal Models and Human Disease Mechanisms,KunmingInstituteofZoology,Chinese Academy of Sciences, Kunming650223,Yunnan, China |
| 推荐引用方式 GB/T 7714 | Xu XQ,Francischetti IMB,Lai R[*],et al. Structure of Protein Having Inhibitory Disintegrin and Leukotriene Scavenging Functions Contained in Single Domain[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(14):10967-10976. |
| APA | Xu XQ,Francischetti IMB,Lai R[*],Ribeiro JMC,&Andersen JF[*].(2012).Structure of Protein Having Inhibitory Disintegrin and Leukotriene Scavenging Functions Contained in Single Domain.JOURNAL OF BIOLOGICAL CHEMISTRY,287(14),10967-10976. |
| MLA | Xu XQ,et al."Structure of Protein Having Inhibitory Disintegrin and Leukotriene Scavenging Functions Contained in Single Domain".JOURNAL OF BIOLOGICAL CHEMISTRY 287.14(2012):10967-10976. |
入库方式： OAI收割
来源：昆明动物研究所
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