• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

仓鼠 P-糖蛋白跨膜螺旋 5 附近的赖氨酸 268 是碘霉素在 CHO B30 细胞中的主要光结合位点。

Lysine 268 adjacent to transmembrane helix 5 of hamster P-glycoprotein is the major photobinding site of iodomycin in CHO B30 cells.

机构信息

Klinische Forschergruppe, Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, Medizinische Hochschule Hannover, Germany.

Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore.

出版信息

FEBS Open Bio. 2021 Apr;11(4):1084-1092. doi: 10.1002/2211-5463.13112. Epub 2021 Feb 28.

DOI:10.1002/2211-5463.13112
PMID:33565718
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8016128/
Abstract

P-glycoprotein (Pgp) detoxifies cells by exporting hundreds of chemically dissimilar hydrophobic and amphipathic compounds and is implicated in multidrug resistance (MDR) in the treatment of cancers. Photoaffinity labeling of plasma membrane vesicles of MDR CHO B30 cells with the anthracycline [ I]-iodomycin, subsequent sequential cleavage with BNPS-skatol and endoproteinase Lys-C, and the Edman sequencing of the purified photoaffinity-labeled peptide identified the lysine residue at position 268 in the hamster Pgp primary sequence as the major photobinding site of iodomycin in CHO B30 cells. Lysine 268 is located adjacent to the cytosolic terminus of transmembrane 5. According to thermodynamic and kinetic analyses, this location should present the equilibrium binding site of ATP-free Pgp for daunomycin and iodomycin in B30 cells.

摘要

P-糖蛋白（Pgp）通过将数百种化学上不同的疏水性和亲脂性化合物输出细胞来解毒，并且与癌症治疗中的多药耐药性（MDR）有关。用蒽环类抗生素[I]-碘柔红霉素对 MDR CHO B30 细胞的质膜囊泡进行光亲和标记，随后用 BNPS-skatol 和内肽酶 Lys-C 进行顺序切割，以及纯化的光亲和标记肽的 Edman 测序，确定了仓鼠 Pgp 一级序列中位于位置 268 的赖氨酸残基为 CHO B30 细胞中碘柔红霉素的主要光结合位点。赖氨酸 268 位于跨膜 5 的胞质末端附近。根据热力学和动力学分析，该位置应呈现 B30 细胞中无 ATP 的 Pgp 与柔红霉素和碘柔红霉素的平衡结合位点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/d295c3e16994/FEB4-11-1084-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/1cfad3d672b4/FEB4-11-1084-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/5e8e70e3d629/FEB4-11-1084-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/dbde8b6b8151/FEB4-11-1084-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/d295c3e16994/FEB4-11-1084-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/1cfad3d672b4/FEB4-11-1084-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/5e8e70e3d629/FEB4-11-1084-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/dbde8b6b8151/FEB4-11-1084-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0b/8016128/d295c3e16994/FEB4-11-1084-g001.jpg

相似文献

1
Lysine 268 adjacent to transmembrane helix 5 of hamster P-glycoprotein is the major photobinding site of iodomycin in CHO B30 cells.仓鼠 P-糖蛋白跨膜螺旋 5 附近的赖氨酸 268 是碘霉素在 CHO B30 细胞中的主要光结合位点。
FEBS Open Bio. 2021 Apr;11(4):1084-1092. doi: 10.1002/2211-5463.13112. Epub 2021 Feb 28.
2
Localization of the iodomycin binding site in hamster P-glycoprotein.碘霉素在仓鼠P-糖蛋白中的结合位点定位
J Biol Chem. 1997 Aug 15;272(33):20913-9. doi: 10.1074/jbc.272.33.20913.
3
Iodomycin and iodipine, a structural analogue of azidopine, bind to a common domain in hamster P-glycoprotein.碘霉素和叠氮平的结构类似物碘地平，与仓鼠P-糖蛋白中的一个共同结构域结合。
Eur J Biochem. 1999 Sep;264(3):800-5. doi: 10.1046/j.1432-1327.1999.00702.x.
4
Equilibrium, kinetic and photoaffinity labeling studies of daunomycin binding to P-glycoprotein-containing membranes of multidrug-resistant Chinese hamster ovary cells.柔红霉素与多药耐药中国仓鼠卵巢细胞含P-糖蛋白膜结合的平衡、动力学及光亲和标记研究。
Eur J Biochem. 1989 Jul 15;183(1):189-97. doi: 10.1111/j.1432-1033.1989.tb14912.x.
5
Effect of anthracycline analogs on photolabelling of p-glycoprotein by [125I]iodomycin and [3H]azidopine: relation to lipophilicity and inhibition of daunorubicin transport in multidrug resistant cells.蒽环类类似物对[125I]碘霉素和[3H]叠氮平光标记P-糖蛋白的影响：与亲脂性及对多药耐药细胞中柔红霉素转运的抑制作用的关系
Br J Cancer. 1993 Feb;67(2):226-31. doi: 10.1038/bjc.1993.44.
6
Identification and localization of three photobinding sites of iodoarylazidoprazosin in hamster P-glycoprotein.碘芳基叠氮哌唑嗪在仓鼠P-糖蛋白中三个光结合位点的鉴定与定位
Eur J Biochem. 2001 May;268(9):2629-34. doi: 10.1046/j.1432-1327.2001.02155.x.
7
Synthetic and natural opiates interact with P-glycoprotein in multidrug-resistant cells.合成及天然阿片类药物与多药耐药细胞中的P-糖蛋白相互作用。
J Biol Chem. 1993 Jul 25;268(21):16059-64.
8
Competitive inhibition of photoaffinity labelling of P-glycoprotein by anticancer drugs and modulators including S9788.抗癌药物和包括S9788在内的调节剂对P-糖蛋白光亲和标记的竞争性抑制作用
Eur J Pharmacol. 1996 Nov 21;315(3):339-43. doi: 10.1016/s0014-2999(96)00616-4.
9
Multiple transport-active binding sites are available for a single substrate on human P-glycoprotein (ABCB1).人 P-糖蛋白（ABCB1）上单个底物有多个转运活性结合位点。
PLoS One. 2013 Dec 5;8(12):e82463. doi: 10.1371/journal.pone.0082463. eCollection 2013.
10
Photoaffinity substrates for P-glycoprotein.P-糖蛋白的光亲和性底物
Biochem Pharmacol. 1992 Jan 9;43(1):89-93. doi: 10.1016/0006-2952(92)90665-6.

本文引用的文献

1
Theoretical insights on helix repacking as the origin of P-glycoprotein promiscuity.作为 P-糖蛋白混杂性起源的螺旋重排的理论见解。
Sci Rep. 2020 Jun 17;10(1):9823. doi: 10.1038/s41598-020-66587-5.
2
FRET analyses reveal a role of ATP hydrolysis-associated conformational changes in human P-glycoprotein.荧光共振能量转移分析揭示了人 P-糖蛋白中与 ATP 水解相关的构象变化的作用。
J Biol Chem. 2020 Apr 10;295(15):5002-5011. doi: 10.1074/jbc.RA119.012042. Epub 2020 Feb 28.
3
Mechanism of allosteric modulation of P-glycoprotein by transport substrates and inhibitors.
转运底物和抑制剂对 P-糖蛋白变构调节的作用机制。
Science. 2019 May 17;364(6441):689-692. doi: 10.1126/science.aav9406.
4
Structural insight into substrate and inhibitor discrimination by human P-glycoprotein.人 P 糖蛋白对底物和抑制剂的选择性的结构见解。
Science. 2019 Feb 15;363(6428):753-756. doi: 10.1126/science.aav7102.
5
Inward- and outward-facing X-ray crystal structures of homodimeric P-glycoprotein CmABCB1.同源二聚体 P-糖蛋白 CmABCB1 的内、外翻 X 射线晶体结构。
Nat Commun. 2019 Jan 8;10(1):88. doi: 10.1038/s41467-018-08007-x.
6
Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation.人 P-糖蛋白在 ATP 结合、向外开放构象下的分子结构。
Science. 2018 Feb 23;359(6378):915-919. doi: 10.1126/science.aar7389. Epub 2018 Jan 25.
7
Global alteration of the drug-binding pocket of human P-glycoprotein (ABCB1) by substitution of fifteen conserved residues reveals a negative correlation between substrate size and transport efficiency.通过替换15个保守残基对人P-糖蛋白（ABCB1）的药物结合口袋进行全局改变，揭示了底物大小与转运效率之间的负相关。
Biochem Pharmacol. 2017 Nov 1;143:53-64. doi: 10.1016/j.bcp.2017.07.014. Epub 2017 Jul 17.
8
Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein.药物与蛋白质的氢键作用调控多药转运蛋白P-糖蛋白的ATP水解抑制作用。
Biochem Pharmacol. 2016 Feb 1;101:40-53. doi: 10.1016/j.bcp.2015.12.007. Epub 2015 Dec 11.
9
Mapping the Binding Site of the Inhibitor Tariquidar That Stabilizes the First Transmembrane Domain of P-glycoprotein.绘制稳定P-糖蛋白第一跨膜结构域的抑制剂塔里喹达的结合位点图谱。
J Biol Chem. 2015 Dec 4;290(49):29389-401. doi: 10.1074/jbc.M115.695171. Epub 2015 Oct 26.
10
Molecular basis of the polyspecificity of P-glycoprotein (ABCB1): recent biochemical and structural studies.P-糖蛋白（ABCB1）多特异性的分子基础：近期的生化与结构研究
Adv Cancer Res. 2015;125:71-96. doi: 10.1016/bs.acr.2014.10.003. Epub 2015 Jan 8.