Converse Conformational Control of Smoothened Activity by Structurally Related Small Molecules
文献类型：期刊论文
| 作者 | Yang, HB; Xiang, J; Wang, ND; Zhao, Y; Hyman, J; Li, S; Jiang, J; Chen, JK; Yang, Z; Lin, S |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2009 |
| 卷号 | 284期号:31页码:20876-20884 |
| 通讯作者 | Yang, Z (reprint author), Peking Univ, Shenzhen Grad Sch, Lab Chem Genom, Shenzhen 518055, Peoples R China.,zyang@pku.edu.cn ; shuolin@ucla.edu |
| 英文摘要 | The seven-pass transmembrane protein Smoothened (Smo) is an essential component of the Hedgehog (Hh) signaling pathway that is critically involved in normal animal development as well as pathological malignancies. In studying Hh-related biological processes, it would be highly desirable if Smo activity could be instantly switched between activation and inhibition. Using Gli1-dependent GFP transgenic zebrafish and in vitro biochemical assays, we identified and characterized two potent Smo inhibitors, SANT74 and 75 (Smoothened antagonist 74 and 75), by screening a small molecule library designed based on the scaffold of Smo agonist SAG. These compounds are structural analogs of SAG with the methyl group substituted by a propyl or allyl group in SANTs. We show that SANTs and SAG exert opposite effects on Smo activity by regulating protein conformation. Our study represents the first demonstration of conformational regulation of Smo by small molecule analogs, and the combinational use of these Smo modulators in a temporal controlled fashion should be useful for studying Hh biology. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | HEDGEHOG SIGNALING PATHWAY ; BASAL-CELL CARCINOMA ; SONIC HEDGEHOG ; HUMAN HOMOLOG ; BRAIN-TUMORS ; FLOOR PLATE ; MEDULLOBLASTOMA ; INHIBITION ; PROLIFERATION ; CYCLOPAMINE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000268316100051 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1288]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Yang, HB,Xiang, J,Wang, ND,et al. Converse Conformational Control of Smoothened Activity by Structurally Related Small Molecules[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2009,284(31):20876-20884. |
| APA | Yang, HB.,Xiang, J.,Wang, ND.,Zhao, Y.,Hyman, J.,...&Lin, S.(2009).Converse Conformational Control of Smoothened Activity by Structurally Related Small Molecules.JOURNAL OF BIOLOGICAL CHEMISTRY,284(31),20876-20884. |
| MLA | Yang, HB,et al."Converse Conformational Control of Smoothened Activity by Structurally Related Small Molecules".JOURNAL OF BIOLOGICAL CHEMISTRY 284.31(2009):20876-20884. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。