HCV NS5B protein aptamer



Description

In 2003, Lai, M. M et al. used the SELEX method to select the aptamer with high compatibility for the Hepatitis C virus NS5B protein. They found that the aptamers can act as templates for HCV polymerase, but others can interfere with the activity of the viral enzyme. These findings suggest that these RNA aptamers may be useful for further characterization of the binding properties of NS5B, and with further modifications, may have potential therapeutic value[1].



SELEX

In 2003, Lai, M. M et al. used an RNA library containing an estimated 1012 distinct RNA species. After 20 screening rounds, the highest RNA enrichment occurred between rounds 18 and 20. Through the SELEX process, 37 ligands were identified and grouped into eight categories (A-H) based on sequence homology[1].

Detailed information are accessible on SELEX page.



Structure

The 2D structure of the figures are based on the article by ribodraw tool to draw. R20-43 apatamer and R20-15 aptamer bind to hepatitis C virus NS5B protein (HCV NS5B protein). R20-43 and R20-15 aptamer was named by Lai, M. M et al[1].

R20-43 aptamer: 5'-GGGAGCUCAGAAUAAACGCUCAAUGUAGAGACUUUUCGAAAAGCGUGUUCCCAAUGAGUCUAUGCAUGCAUGAGGCCCGGAUCCGGC-3'
R20-15 aptamer: 5'-GGGAGCUCAGAAUAAACGCUCAAUGUAGGCUAGUACCGACCUGCGUGCCUCGCUCCUUUUCAUGCAUGCAUGAGGCCCGGAUCCGGC-3'

drawing drawing


Ligand information

SELEX ligand

Some isolated sequences bind to the affinity of the protein[1].

Name Sequence Ligand Affinity
R20-43 5'-GGGAGCUCAGAAUAAACGCUCAAUGUAGAGACUUUUCGAAAAGCGUGUUCCCAAUGAGUCUAUGCAUGCAUGAGGCCCGGAUCCGGC-3' HCV NS5B protein 1.4 ± 0.3 (1/s)
R20-15 5'-GGGAGCUCAGAAUAAACGCUCAAUGUAGGCUAGUACCGACCUGCGUGCCUCGCUCCUUUUCAUGCAUGCAUGAGGCCCGGAUCCGGC-3' HCV NS6B protein 1.0 ± 0.1 (1/s)
R1-1 5'-GGGAGCUCAGAAUAAACGCUCAACUCCUAACCUCUCCGCAUGNGCUGUUACCUACACAGCUCAGCAUGCAUGAGGCCCGGAUCCGGC-3' HCV NS7B protein 100 ± 6 (1/s)
drawing

Structure ligand

This family includes viral RNA dependent RNA polymerase enzymes from hepatitis C virus and various plant viruses.-----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
Hepatitis C virus NS5B protein (HCV NS5B protein) P26663 PF00998 58.978 kDa
...... SMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAGLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSAKSKFGYGAKDVRNLSSKAVNHIHSVWKDLLEDTVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSTLPQVVMGSSYGFQYSPGQRVEFLVNTWKSKKNPMGFSYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIKSLTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSAFSLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRARLLSQGGRAATCGKYLFNWAVK
1CSJ M58335

Similar compound(s)

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.

Dail server website: a network service for comparing protein structures in 3D. Dali compares them against those in the Protein Data Bank (PDB).

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
1CSJ-A 61.3 0 Hepatitis C virus RNA polymerase (ns5b)
1CSJ-B 60.0 0.2 Hepatitis C virus RNA polymerase (ns5b)
1GX5-A 57.6 0.4 RNA-directed RNA polymerase
2WRM-A 57.2 0.4 RNA-directed RNA polymerase
2WHO-A 57.2 0.4 RNA-directed RNA polymerase
1GX6-A 57.1 0.4 RNA-directed RNA polymerase
2WHO-B 57.0 0.4 RNA-directed RNA polymerase
2WCX-A 54.8 0.6 RNA-directed RNA polymerase
2BRK-A 54.7 0.6 RNA-directed RNA polymerase
2BRL-A 54.3 0.6 RNA-directed RNA polymerase


References

[1] Identification of RNA ligands that bind hepatitis C virus polymerase selectively and inhibit its RNA synthesis from the natural viral RNA templates.
Vo, N. V., Oh, J. W., & Lai, M. M.
Virology, 307(2), 301–316. (2003)