Lysine-specific demethylase 6 homolog (SmKDM6) (SmKDM6)

The Schistosoma mansoni KDM6 homolog (SmKDM6) is a JmjC domain-containing histone demethylase that plays a pivotal role in the epigenetic regulation of the parasite's life cycle (Roquis et al., 2015, PLOS Negl Trop Dis). It specifically targets the demethylation of tri-methylated and di-methylated lysine 27 on histone H3 (H3K27me3/2), a modification generally associated with transcriptional repression (WormBase ParaSite, Gene: Smp_136180). By modulating these epigenetic marks, SmKDM6 influences gene expression programs necessary for the development, maturation, and reproductive success of the blood fluke. Given its essentiality for parasite survival and egg laying—the latter being the primary driver of schistosomiasis-related morbidity—SmKDM6 has emerged as a promising anthelmintic drug target (Shiao et al., 2020, ACS Infect Dis). Experimental studies using the small-molecule inhibitor GSK-J4 have shown that blocking SmKDM6 activity results in impaired worm motility and a drastic reduction in egg output. However, the high structural conservation between SmKDM6 and its human counterparts, KDM6A (UTX) and KDM6B (JMJD3), necessitates the development of highly selective inhibitors to minimize potential host toxicity. Consequently, SmKDM6 represents a key focus in the search for next-generation epigenetic therapies against schistosomiasis.

Other names

SmKDM6SmUTXSmJMJD3Smp_136180Schistosoma mansoni KDM6JmjC domain-containing protein

Inhibition of the JmjC domain-mediated demethylation of tri-methylated and di-methylated lysine 27 on histone H3 (H3K27me3/me2).