Home
Database
Research
About us
PAI-1 aptamer
Timeline
Active PAI-1 effectively inhibits target proteases but is labile as it spontaneously converts to the latent form[1]
Active PAI-1 binds to the extracellular matrix protein, vitronectin, which is unable to bind inactive PAI-1 or PAI-1 in complex with its target proteases[2]
PAI-1 competes with integrins and uPAR for vitronectin binding, resulting in the detachment of cells from the extracellular matrix[3]
The binding of PAI-1 to vitronectin prevents integrins from binding to vitronectin and inhibits cell adhesion in some cells, particularly breast cancer cells[4]
PAI-1 has been proven responsible for the regulation of cellular adhesion and migration, and has been shown to interact with several extracellular matrix components[5]
Description
In 2009, Charlene M Blake et al. used the SELEX method to isolate the aptamer with high compatibility for the serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1). They determined that aptamers WT-15 binds to PAI-1 in a region that spans the heparin- and vitronectin-binding domains, inhibiting the PAI-1/vitronectin interaction. The PAI-1 aptamer WT-15 demonstrates therapeutic potential as an antimetastatic agent and could possibly be used as an adjuvant to traditional chemotherapy for breast cancer[6].SELEX
In 2009, Charlene M Blake et al. generated aptamers that specifically bind to PAI-1 with high affinity (Kd < 4 nM) using SELEX . Through functional assays including mutagenesis studies, competition binding, chromogenic assays, and cell adhesion experiments, they determined that aptamers WT-15 binds to PAI-1 in a region that spans the heparin- and vitronectin-binding domains, inhibiting the PAI-1/vitronectin interaction[6].
Detailed information are accessible on SELEX page.
Structure
The 2D structure of the figure is based on the prediction results of the RNA fold website by ribodraw tool to draw.5'-GGGAGGACGAUGCGGAUCAACUCACCGUAGGUCUAGUGAGAACUUCAAGUCUACUCAGACGACUCGCUGAGGAUCC-3'
Ligand information
SELEX ligand
Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor (serpin E1) is a protein that in humans is encoded by the SERPINE1 gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis. PAI-1 is a serine protease inhibitor (serpin) that functions as the principal inhibitor of tissue-type plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis (the physiological breakdown of blood clots). It is a serine protease inhibitor (serpin) protein (SERPINE1).-----From Wiki
| Name | Uniprot ID | Pfam | MW | Amino acids sequences | PDB | Gene ID |
|---|---|---|---|---|---|---|
| Serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1) | P05121 | IPR000215 | 45.07 kDa | MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPYGVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAIFVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAVDQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPDGHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPKFSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASSSTAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP | 4DTE | 5054 |
Some isolated sequences bind to the affinity of the protein.
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| WT-15 | 5'-GGGAGGACGAUGCGGAUCAACUCACCGUAGGUCUAGUGAGAACUUCAAGUCUACUCAGACGACUCGCUGAGGAUCC-3' | Serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1) | 177 pM |
Similar compound
We used the Dail server website to compare the structural similarities of ligand proteins, and chose the top 10 in terms of similarity for presentation. The Dali server is a network service for comparing protein structures in 3D. Dali compares them against those in the Protein Data Bank (PDB). Z-score is a standard score that is converted from an original score. The list of neighbours is sorted by Z-score. Similarities with a Z-score lower than 2 are spurious. RMSD(Root Mean Square Deviation) value is used to measure the degree to which atoms deviate from the alignment position.
| PDB | Z-socre | RMSD | Description |
|---|---|---|---|
| 4DY0-B | 50.5 | 1.7 | Glia-derived nexin |
| 4DY7-F | 50.1 | 2.0 | Thrombin light chain |
| 4DY7-C | 50.1 | 1.9 | Thrombin light chain |
| 3Q03-B | 50.0 | 1.3 | Plasminogen activator inhibitor 1 |
| 3Q02-A | 49.9 | 1.3 | Plasminogen activator inhibitor 1 |
| 6GWN-A | 49.6 | 1.4 | Plasminogen activator inhibitor 1 |
| 3Q03-A | 49.6 | 1.4 | Plasminogen activator inhibitor 1 |
| 4G8R-A | 49.4 | 1.4 | Plasminogen activator inhibitor 1 |
| 3PB1-I | 49.4 | 1.6 | Plasminogen activator inhibitor 1 |
| 1DB2-A | 49.4 | 1.6 | Plasminogen activator inhibitor 1 |
References
[1] Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants.Hekman, C. M., & Loskutoff, D. J.
The Journal of biological chemistry, 260(21), 11581–11587. (1985)
[2] Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin).
Declerck, P. J., De Mol, M., Alessi, M. C., Baudner, S., Pâques, E. P., Preissner, K. T., Müller-Berghaus, G., & Collen, D.
The Journal of biological chemistry, 263(30), 15454–15461. (1988)
[3] Structural and functional analysis of the plasminogen activator inhibitor-1 binding motif in the somatomedin B domain of vitronectin.
Deng, G., Royle, G., Wang, S., Crain, K., & Loskutoff, D. J.
The Journal of biological chemistry, 271(22), 12716–12723. (1996)
[4] Plasminogen activator inhibitor-1 represses integrin- and vitronectin-mediated cell migration independently of its function as an inhibitor of plasminogen activation.
Kjøller, L., Kanse, S. M., Kirkegaard, T., Rodenburg, K. W., Rønne, E., Goodman, S. L., Preissner, K. T., Ossowski, L., & Andreasen, P. A.
Experimental cell research, 232(2), 420–429. (1997)
[5] Plasminogen activator inhibitor type-1: its structure, biological activity and role in tumorigenesis (Review).
Chorostowska-Wynimko, J., Skrzypczak-Jankun, E., & Jankun, J.
International journal of molecular medicine, 13(6), 759–766. (2004)
[6] Antimetastatic potential of PAI-1-specific RNA aptamers.
Blake, C. M., Sullenger, B. A., Lawrence, D. A., & Fortenberry, Y. M.
Oligonucleotides, 19(2), 117–128. (2009)