Mapping Dihydropteroate Synthase Evolvability Through Identification of a Novel Evolutionarily Critical Substructure

Overview

Dihydropteroate synthase (DHPS) is the target of sulfa-based antimalarial and antimicrobial drugs, and mutations in DHPS underlie clinically important sulfadoxine resistance. This project investigated the evolutionary constraints acting on DHPS, asking which regions of the protein are free to vary and which are evolutionarily "locked" by structural or functional necessity.

Through structural and evolutionary analysis, we identified a previously uncharacterised substructure that is critical to DHPS evolvability — a conserved region whose constraints shape how the protein can (and cannot) adapt, and which represents a candidate site for future drug targeting.

Key Highlights

• Identification of a novel, evolutionarily critical DHPS substructure
• Structural mapping of conserved versus variable regions across DHPS homologues
• Links evolutionary constraint analysis to future antimalarial drug-target discovery
• Published in the International Journal of Biological Macromolecules (IF 7.7)