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HIV-1 integrase aptamer
Description
In 1995, Gold, L. and colleagues were able to isolate high-affinity RNAs from a random pool that binds to integrase protein from the human immunodeficiency virus-type 1 using the procedure now known as SELEX. Generally, the RNAs fell into three different classes in binding buffer containing 250 mM NaCl: group I class of molecules binds integrase with a dissociation constant (Kd) on the order of 10 nM, group II molecules had a Kd of about 80 nM, and group III about 800 nM. The RNA with the highest affinity from the group I class of molecules, designated P5, was characterized using computer modeling, chemical and enzymatic probing, and deletion analysis[1].
SELEX
In 1995, Gold, L. 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. The P5 aptamer was named by Gold, L. et al. in the article[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
UniProt ID: uniquely identifies protein sequences in the UniProt database, a resource for protein information.
Pfam: a widely recognised database of protein families and domains.
GenBank: maintained by NCBI(National Center for Biotechnology Information), is a database of nucleotide sequences from various organisms, vital for genetic and molecular biology research.
Mass: an intrinsic property of a body.
| Name | Uniprot ID | Pfam | Mass | Protein sequence | PDB ID | GenBank |
|---|---|---|---|---|---|---|
| HIV-1 integrase | Q76353 | PF00665 | 15.44 kDa |
......
CSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTVHTDNGSNFTSTTVKTACWWAGIKQEFGIESMNKELKKIIGQVRDQAEHLQTAVQMAVFIHNKKRKGGYSAGERIVDIIATDI
|
6L0C | AAC37875.1 |
Some isolated sequences bind to the affinity of the protein[1].
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| P5 | 5'-GGGAGCUCAGAAUAAACGCUCAACCAGUCUUGUGGCUUUGAAAGAGAGGAGUGUUCGACAUGAGGCCCGGAUCCGGC-3' | HIV-1 integrase | 2-12 nM |
| A54 | 5'-GGGAGCUCAGAAUAAACGCUCAACGGCACAGGGGUUGUAUCCUCCGGGACGAAUUCGACAUGAGGCCCGGAUCCGGC-3' | HIV-1 integrase | ~80.0 nM |
Similar compound(s)
We used the RCSB PDB website's similar structure search to find the top 10 structures similar to HIV-1 REV PROTEIN (residues T34-R50), and calculated TM-socre values and RMSD values using the TM-align website.
Z-score: 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) is used to measure the degree to which atoms deviate from the alignment position.
PDB: PDB ID+ chain name.
| PDB | Z-socre | RMSD (Å) | Description |
|---|---|---|---|
| 6L0C-A | 29.6 | 0 | Integrase |
| 4JLH-A | 26.5 | 0.5 | HIV-1 integrase catalytic core domain |
| 1B92-A | 26.5 | 0.8 | Protein (integrase) |
| 4O55-A | 26.5 | 0.6 | Integrase |
| 5HRR-A | 26.4 | 0.4 | Integrase |
| 1BIZ-A | 26.4 | 0.7 | HIV-1 integrase |
| 1B9D-A | 26.4 | 0.7 | Protein (integrase) |
| 1HYV-A | 26.3 | 0.8 | Integrase |
| 5KGW-A | 26.3 | 0.5 | Integrase |
| 4O0J-A | 26.2 | 0.7 | Integrase |
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)