DHPS: Dihydropteroate synthase (DHPS) is an essential bacterial enzyme that makes dihydropteroate, and it is absent in humans. In Mycobacterium leprae, DHPS is encoded by the folP1 gene (ML0224), and mutations in folP1 are associated with resistance to dapsone, a bacteriostatic drug in multidrug therapy for leprosy. HARP contains only missense mutations, represented as amino acid substitutions at each residue position in the DHPS structure. The structural impacts of all 19 possible substitutions at each position are computed with a range of predictive algorithms. See the Help page for more information. 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. T53I). Press "Mutation Results" to list them and open any mutation on HARP.
3D Visualisation of the Dapsone-Binding Site in DHPS and the Chemical Structure of Dapsone
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 dapsone with the surrounding residue environment in chain 'A' of wild-type DHPS. Hydrogen bonds (blue), weak hydrogen bonds (light blue) and metal interactions (purple) are shown.
Dapsone in 3D
Structure: PubChem 3D conformer.
Note: Hold the left mouse button and move to see the structure of Dapsone in 3D. Scroll to zoom.
Predict the pharmacokinetic properties of Dapsone.