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SUMMARY:Macromolecular X-ray Crystallography Studies of S. mansoni GAPDH i
 n the Discovery  and Design of Novel Anti-Schistosomal Compounds
DTSTART;VALUE=DATE-TIME:20260608T170000Z
DTEND;VALUE=DATE-TIME:20260608T173000Z
DTSTAMP;VALUE=DATE-TIME:20260606T094359Z
UID:indico-contribution-10353@events.saip.org.za
DESCRIPTION:Speakers: Naledi Pilusa (University of johannesburg)\nMacromol
 ecular X-ray crystallography is a powerful\, sensitive technique that allo
 ws the identification of ligand-protein complexes\, but it depends on crys
 tals of high resolution and high tolerance to inorganic solvents. In this 
 study\, we investigated possible alternatives to the sole treatment of sch
 istosomiasis\, Praziquantel\, by identifying small molecules that can inte
 ract with *Schistosoma* *mansoni* Glyceraldehyde-3-phosphate dehydrogenase
  (SmGAPDH). Identified in all life stages of parasitic worms causing schis
 tosomiasis\, a chronic parasitic disease of poverty that causes significan
 t morbidity and mortality\, accounting for 70 million disability-adjusted 
 life years lost annually. SmGAPDH is characterised as a potential therapeu
 tic target that plays a pivotal role in the parasite’s evasion of the hu
 man host and correlates with drug resistance. For this part of the study\,
  full-length SmGAPDH was produced in Escherichia coli cells\, purified to 
 homogeneity using immobilised-nickel affinity chromatography and size-excl
 usion chromatography\, and subjected to crystallisation trials. X-ray diff
 raction data were collected and used to analyse the electron density map\,
  conduct structural analysis and functional studies\, and run fragment scr
 eening. The full-length SmGAPDH was successfully purified and formed cryst
 als within 24 hours under Morpheus and ShotGun1 screening\, yielding high-
 resolution X-ray diffraction data at 1.8 Å and reproducible 2.5 Å data i
 n the presence of DMSO. Evaluation of the electron density map shows a den
 sity for NAD+\, unobserved in the previous studies. A life soak test ident
 ified 12 binding pockets and 5 potential ligands. These findings provide a
  fundamental structural basis for applying crystallographic screening to d
 etermine the functional aspects of SmGAPDH exploitable in fragment-based d
 rug discovery and design\, while prioritising the NAD-binding site.\n\nhtt
 ps://events.saip.org.za/event/274/contributions/10353/
LOCATION:
URL:https://events.saip.org.za/event/274/contributions/10353/
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