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P5 aptamer
Description
In 1995, Patrick Allen and colleagues used the SELEX method to isolate the aptamer with high affinity for the HIV-1 integrase. The aptamer will competitively inhibit interaction between integrase and viral DNA and thus may prevent formation of preintegration complexes and viral DNA processing[1].SELEX
In 1995, Patrick Allen et al. constructed a random pool, the random pool of DNA oligomers was synthesized in which the 5'- and 3'-proximal ends were fixed sequences used for amplification and the central region consisted of 30 randomized positions. After 18 rounds of SELEX, RNA sequences with high specificity were selected[1].
Detailed information are accessible on SELEX page.
Structure
P5 was the aptamer sequence mainly studied in the article, which had a high affinity with HIV-1 integrase. The 2D structure of the figure is based on the article by ribodraw tool to draw[1].5'-GGGAGCUCAGAAUAAACGCUCAACCAGUCUUGUGGCUUUGAAAGAGAGGAGUGUUCGACAUGAGGCCCGGAUCCGGC-3'
Ligand information
SELEX ligand
Integrase mediates integration of a DNA copy of the viral genome into the host chromosome. Integrase is composed of three domains. The amino-terminal domain is a zinc binding domain. This domain is the central catalytic domain. The carboxyl terminal domain that is a non-specific DNA binding domain. The catalytic domain acts as an endonuclease when two nucleotides are removed from the 3' ends of the blunt-ended viral DNA made by reverse transcription. This domain also catalyses the DNA strand transfer reaction of the 3' ends of the viral DNA to the 5' ends of the integration site.-----From Pfam
| Name | Uniprot ID | Pfam | MW | Amino acids sequences | PDB | Gene ID |
|---|---|---|---|---|---|---|
| HIV-1 integrase | Q76353 | PF00665 | 15.44 kDa | CSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTVHTDNGSNFTSTTVKTACWWAGIKQEFGIESMNKELKKIIGQVRDQAEHLQTAVQMAVFIHNKKRKGGYSAGERIVDIIATDI | 6L0C | AAC37875.1 |
Some isolated sequences bind to the affinity of the protein.
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| P5 | GGGAGCUCAGAAUAAACGCUCAACCAGUCUUGUGGCUUUGAAAGAGAGGAGUGUUCGACAUGAGGCCCGGAUCCGGC | HIV-1 integrase | 2-12 nM |
| A54 | GGGAGCUCAGAAUAAACGCUCAACGGCACAGGGGUUGUAUCCUCCGGGACGAAUUCGACAUGAGGCCCGGAUCCGGC | HIV-1 integrase | ~80.0 nM |
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 |
|---|---|---|---|
| 6RWL-A | 20.0 | 1.3 | Pol protein |
| 6Z2Y-B | 15.9 | 2.2 | Pol protein |
| 3OY9-A | 15.0 | 2.7 | Pfv integrase |
| 5EJK-D | 14.7 | 2.2 | Gag-pro-pol polyprotein |
| 8B4H-C | 13.3 | 2.3 | Putative transposase for insertion sequence eleme |
| 4FCY-B | 12.4 | 2.5 | Transposase |
| 8EA3-W | 12.0 | 2.6 | Target_le |
| 7Q5B-B | 11.7 | 2.9 | DNA (56-mer) |
| 5CR4-B | 9.7 | 2.8 | Sleeping beauty transposase, SB100X |
| 4U7B-A | 8.5 | 3.2 | DNA (25-mer) |
References
[1] Isolation of high-affinity RNA ligands to HIV-1 integrase from a random pool.Allen, P., Worland, S., & Gold, L.
Virology, 209(2), 327–336. (1995)