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SUMMARY:Production of Leishmania spp. ∆24-sterol methyltransferases for 
 the development of antiparasitic therapies
DTSTART;VALUE=DATE-TIME:20260326T124500Z
DTEND;VALUE=DATE-TIME:20260326T130500Z
DTSTAMP;VALUE=DATE-TIME:20260425T232449Z
UID:indico-contribution-10325@events.saip.org.za
DESCRIPTION:Speakers: Bernadette Belter ()\nParasitic diseases\, such as l
 eishmaniasis\, pose a growing global health threat\, particularly in regio
 ns with high HIV/AIDS prevalence [1]. The limited efficacy and growing res
 istance to current treatments necessitate the discovery of novel therapeut
 ic targets. ∆24-sterolmethyltransferase (SMT) is an attractive target as
  an essential enzyme in the ergosterol biosynthetic pathway of protozoa an
 d has no mammalian homologue [2]. SMT catalyses the transfer of a methyl g
 roup from S-adenosyl-methionine to the C24 position of zymosterol or lanos
 terol [3]. Structural characterisation of SMTs via X-ray crystallography i
 s crucial for structure-based drug discovery approaches. This study aims t
 o produce and structurally characterise SMTs from *Leishmania* *donovani* 
 and *Leishmania major* to identify lead compounds for antiparasitic therap
 ies.\nThe *ERG6* genes\, encoding SMT\, from *L. donovani* and *L. major* 
 were expressed in *E. coli*\, but resulted in insoluble protein. We then f
 used ERG6 to genes encoding mCherry or SUMO and successfully expressed the
  fusions as soluble proteins. The SMTs were cleaved from the fusion partne
 rs and purified using column chromatography methods.   Furthermore\, the p
 urified SMTs have been shown to methylate lanosterol using GC-MS. Biotrans
 formation optimisation is underway to improve conversion yields.\nCrystall
 isation trials using the vapour-diffusion sitting-drop method are currentl
 y ongoing. Future work includes collecting X-ray diffraction data of the S
 MT crystals to solve their three-dimensional structures. The structural in
 formation\, as well as a robust crystal system\, is a prerequisite for X-r
 ay crystallographic fragment screening\, which will be used to map SMT bin
 ding pockets for inhibitor design. \nReferences\n[1] Dangarembizi\, R.\, W
 asserman\, S.\, Hoving\, J. C.\, et al. Parasite Immunology\, (2023) e1295
 3. \n[2] Sakyi\, P. O.\, Kwofie\, S. K.\, Tuekpe\, J. K.\, et al. Pharmace
 uticals\, (2023) 16(3)\, 330.\n[3] Nes\, W.D.\, Chaudhuri\, M.\, Leaver\, 
 D.J. Biomolecules\, (2024) 14:249.\n\nhttps://events.saip.org.za/event/272
 /contributions/10325/
LOCATION:
URL:https://events.saip.org.za/event/272/contributions/10325/
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