DAPSONE - Structural Impacts of Mutations in Dihydropteroate Synthase (DHPS) of Mycobacterium leprae

DHPS: Dihydropteroate Synthase (DHPS) is an essential enzyme for the synthesis of Dihydropteroate in bacteria, and DHPS is absent in the humans. The folp1 gene (ML0224) encodes DHPS in Mycobacterium leprae and mutations within folp1 gene are associated with resistance to dapsone, a bacteriostatic drug in the multi-drug therapy for leprosy. The mutations that are included in the HARP database are only the missense mutations represented by amino acid substitutions at each residue position in the DHPS structure. Structural impacts of all the 19 possible substitutions at each residue position are computed using various predictive algorithms. Please see the HELP page for more information. Submit either single mutations or just the residue positions in the fields below. Additionally, user can upload Ab1 chromatogram files and view results of the BlastX search.

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:T53I. 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:53. Press the help button for more information.)


Upload AB1 File:

Note: Upload AB1 files from DNA 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.

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.


Upload FASTA File

...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. T53I). Press "Mutation Results" to list them and open any mutation on HARP.


3D Visualization of the Dapsone Binding Site in DHPS & Chemical structure of Dapsone

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 dapsone with the surrounding residue environment in chain 'A' of wildtype DHPS. Hydrogen bonds (blue), weak hydrogen bond (light blue) and metal interactions (purple) can be noted.

Dapsone - 3D View

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

Click here to predict Pharmacokinetic Properties of Dapsone.
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 on using Protein Feature Viewer

HARP
Disclaimer: This resource is intended for research use. Please validate findings experimentally and interpret mutations and structural annotations together with clinical and biological context.

HARP is a Leprosy Resource

This material is Open Knowledge