RNAP: RNA polymerase is an essential enzyme that carries out DNA-dependent RNA synthesis in mycobacteria, as in other organisms. The holoenzyme is a heterohexameric complex of six chains (A to F) encoded by the rpoA, rpoA', rpoB, rpoC, rpoD, rpoZ and rpoT genes of Mycobacterium leprae. Mutations in rpoB and rpoC are associated with resistance to rifampicin, a bactericidal drug in multidrug therapy for leprosy. HARP contains only missense mutations, represented as amino acid substitutions at each residue position in every chain of the RNAP structure. All 19 possible substitutions at each residue are analysed with a range of computational tools. Submit a single mutation or a residue position below. You can also upload AB1 chromatogram files or FASTA sequences and view the BLASTX results.
Query Mutations:
Note: Query mutations and residue positions here. See the Help page for more information.
Single Mutation:
Note: Submit a single amino acid substitution identified by translating your sequencing reads.
Systematic Mutations:
Note: Submit a residue position from the modelled region. Select Help for more information.
Upload AB1 File:
Note: Upload AB1 files from Sanger or next-generation sequencing.
Upload FASTA File:
Note: Upload a DNA FASTA sequence. It is translated and searched with BLASTX against the Lep-AMR reference amplicons for rpoB, folP1 and gyrA.
...or paste a DNA sequence (FASTA or plain bases):
Note: Every amino acid difference between the translated query and the reference amplicon is reported as a HARP substitution (e.g. D441Y). Press "Mutation Results" to list them and open any mutation on HARP.
3D Visualisation of the Rifampicin-Binding Site in RNAP and the Chemical Structure of Rifampicin
Note: Hold the left mouse button and move over the viewers to see the structures in 3D. Scroll to zoom.
Interactive 3D Viewer: Interatomic interactions of rifampicin with the surrounding residue environment in chain 'C' of wild-type RNAP. Hydrogen bonds (blue), weak hydrogen bonds (light blue), pi-interactions (orange) and metal interactions (purple) are shown.
Rifampicin in 3D
Structure: bound pose from the HARP RNAP model.
Note: Hold the left mouse button and move to see the structure of Rifampicin in 3D. Scroll to zoom.
Predict the pharmacokinetic properties of Rifampicin.