OFLOXACIN - Structural Impacts of Mutations in DNA Gyrase (GYR) of Mycobacterium leprae

GYR: DNA Gyrase (GYR) is an essential enzyme in mycobacteria that catalyses ATP-dependent transient cleavage and negative supercoiling of closed circular DNA. The heterotetrameric protein (GyrA2, GyrB2) is comprised of four chains (A, B, C, D) which are encoded by gyrA (ML0006) and gyrB (ML0005) in Mycobacterium leprae. Mutations within the GyrA subunit are associated with resistance to ofloxacin, a second-line bactericidal drug in the treatment of 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 GYR structure. All the 19 possible substitutions at each residue position 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.

Note: The GYR model of Mycobacterium leprae is built using PDB ID:5BS8. Chain A has an intein region from residue positions 131-550 which was removed during modelling. The residue numbering is consistent with the template alignment.

Query Mutations:

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

Single Mutation:

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

Drug Target:
Chain:
Mutation:

(E.g:A91V. Press the help button for more information.)

Systematic Mutations:

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

Drug Target:
Chain:
Residue Position:

(E.g:91. Press the help button for more information.)

Upload ABI File:

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

Upload ABI 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 Ofloxacin Binding Site in GYR & Chemical structure of Ofloxacin

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 ofloxacin with the surrounding residue environment in chain 'B' of wildtype GYR. Hydrogen bonds (blue), weak hydrogen bond (light blue) and metal interaction (purple) can be noted.

Ofloxacin - 3D View

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

Click here to predict Pharmacokinetic Properties of Ofloxacin.
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 GyrA (chain-A) is loaded to provide quick access to Quinolone Resistance Determining Region (QRDR) of the GYR Structure. As the intein region from residue numbers 131-550 has been removed in the model, the sequence numbers correspond with the structure from 16-130 and 550-921 (eg: residue position 131 in the model corresponds to sequence number 551 and so on).

HARP is a Leprosy Resource

This material is Open Knowledge