Sulfated polymannuroguluronate inhibits Tat-induced SLK cell adhesion via a novel binding site, a KKR spatial triad
文献类型：期刊论文
| 作者 | Wu, Yan-lin1; Ai, Jing2 ; Zhao, Jing-ming3; Xiong, Bing4; Xin, Xiao-jie2; Geng, Mei-yu2; Xin, Xian-liang2; Jiang, Han-dong3
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2011-05 |
| 卷号 | 32期号:5页码:647-654 |
| 关键词 | sulfated polymannuroguluronate transactivating factor of the HIV-1 virus (Tat) binding site Kaposi's sarcoma heparin mutation HIV-1 |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2011.2 |
| 文献子类 | Article |
| 英文摘要 | Aim: Sulfated polymannuroguluronate (SPMG), a candidate anti-AIDS drug, inhibited HIV replication and interfered with HIV entry into host T lymphocytes. SPMG has high binding affinity for the transactivating factor of the HIV-1 virus (Tat) via its basic domain. However, deletion or substitution of the basic domain affected, but did not completely eliminated Tat-SPMG interactions. Here, we sought to identify other SPMG binding sites in addition to the basic domain. Methods: The potential SPMG binding sites were determined using molecular simulation and a surface plasmon resonance (SPR) based competitive inhibition assay. The effect of SPMG on Tat induced adhesion was evaluated using a cell adhesion assay. Results: The KKR domain, a novel high-affinity heparin binding site, was identified, which consisted of a triad of Lys12, Lys41, and Arg78. The KKR domain, spatially enclosed SPMG binding site on Tat, functions as another binding domain for SPMG. Further functional evaluation demonstrated that SPMG inhibits Tat-mediated SLK cell adhesion by directly binding to the KKR region. Conclusion: The KKR domain is a novel high-affinity binding domain for SPMG. Our findings provide important new insights into the molecular mechanisms of SPMG and a potential therapeutic intervention for Tat-induced cell adhesion. |
| WOS关键词 | HIV-1 TAT ; PROTEIN INTERACTIONS ; HEPARAN-SULFATE ; KAPOSIS-SARCOMA ; DRUG CANDIDATE ; GROWTH-FACTOR ; DOMAIN ; OLIGOSACCHARIDES ; MULTIPLE ; SIZE |
| 资助项目 | National Natural Science Foundation of China[30772884] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4190581 |
| WOS记录号 | WOS:000290276300013 |
| 出版者 | SHANGHAI INST MATERIA MEDICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278545]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Xin, Xian-liang |
| 作者单位 | 1.Ocean Univ China, Sch Med & Pharm, Dept Pharmacol & Glycobiol, Qingdao 266003, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Qingdao Univ, Affiliated Hosp, Div Resp Med, Med Coll, Qingdao 266003, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Yan-lin,Ai, Jing,Zhao, Jing-ming,et al. Sulfated polymannuroguluronate inhibits Tat-induced SLK cell adhesion via a novel binding site, a KKR spatial triad[J]. ACTA PHARMACOLOGICA SINICA,2011,32(5):647-654. |
| APA | Wu, Yan-lin.,Ai, Jing.,Zhao, Jing-ming.,Xiong, Bing.,Xin, Xiao-jie.,...&Jiang, Han-dong.(2011).Sulfated polymannuroguluronate inhibits Tat-induced SLK cell adhesion via a novel binding site, a KKR spatial triad.ACTA PHARMACOLOGICA SINICA,32(5),647-654. |
| MLA | Wu, Yan-lin,et al."Sulfated polymannuroguluronate inhibits Tat-induced SLK cell adhesion via a novel binding site, a KKR spatial triad".ACTA PHARMACOLOGICA SINICA 32.5(2011):647-654. |
入库方式： OAI收割
来源：上海药物研究所
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