RIFAMPICIN - Structural Impacts of Mutations in RNA Polymerase (RNAP) of Mycobacterium leprae

RNAP: RNA Polymerase is an essential enzyme that mediates DNA depended RNA synthesis in mycobacteria as in other organisms. The holoenzyme complex is a heterohexameric protein comprised of six chains (A,B,C,D,E,F) that are encoded by rpoA, rpoA', rpoB, rpoC, rpoD, rpoZ, rpoT genes in Mycobacterium leprae. Mutations within the rpoB and rpoC genes are associated with resistance to rifampin, a bactericidal drug in the multi-drug therapy for leprosy. The mutations that are included in the HARP database are only missense mutations represented by amino acid substitutions at each residue position in all the chains of the RNAP structure. All the 19 possible substitutions for each amino acid residue are analysed using various computational tools. Submit either single mutations or just the residue positions in the fields below. Additionally, user can upload Ab1 chromatogram files and view the Blastx results.

Query Mutations:


Note: Query mutations and residue positions here. Please see the help page for more information.

Single Mutation:

Note: Submit single amino acid substitutions identified by translating the sequencing reads.


Mutation:

(E.g:D441Y. Press the help button for more information.)

Systematic Mutations:

Note: Submit residue positions from the modelled region. Click help button for more information.


Residue Position:

(E.g:441. Press the help button for more information.)


Upload AB1 File:

Note: Upload AB1 files from sanger sequencing or NextGen sequencing.


Upload AB1 File

Note: Once the AB1 chromatogram file is uploaded, it is automatically processed and the results are displayed on pressing the "Processed AB1 File" button above.


3D Visualization of the Rifampicin Binding Site in RNAP & Chemical structure of Rifampicin

Note: Hold left mouse button and hover over the viewers to visualize the structures in 3D. Scroll to zoom.

Interactive 3D Viewer: Interactomic Interactions of rifampicin with the surrounding residue environment in chain 'C' of wildtype RNAP. Hydrogen bonds (blue), weak hydrogen bond (light blue), pi-interactions (orange) and metal interaction (purple) can be noted.

Rifampicin - 3D View

Note: Hold the left mouse click and move to see the structure of Rifampicin in 3D. Scroll to Zoom

Click here to predict Pharmacokinetic Properties of Rifampicin.
Protein Feature Viewer:
Note: The protein feature viewer is implemented to help users to view the sequence based annotations of the drug target. Adjust the scale sliders on the top of the viewer to view the sequence. Please see the help page for more information. Only RpoB (chain-C) is loaded to provide quick access to Rifampin Resistance Determining Region (RRDR) of the RNAP structure.


HARP is a Leprosy Resource

This material is Open Knowledge