Plasmodium falciparum histone acetyltransferase GCN5 (PfGCN5) (PfGCN5)

Plasmodium falciparum histone acetyltransferase GCN5 (PfGCN5) is a critical epigenetic enzyme that regulates gene expression in the malaria parasite by acetylating lysine residues on histone H3, specifically H3K9 and H3K14 [UniProt, https://www.uniprot.org/uniprotkb/Q8I0G2/entry]. This enzymatic activity is essential for the parasite's intraerythrocytic developmental cycle, coordinating the transcription of genes necessary for host cell invasion and environmental adaptation [PubMed, https://pubmed.ncbi.nlm.nih.gov/17513222/]. PfGCN5 operates within a multi-protein complex and is a key player in the parasite's response to stress and developmental cues [PubMed, https://pubmed.ncbi.nlm.nih.gov/28844836/]. As an essential enzyme with structural differences from its human ortholog, PfGCN5 is a high-priority target for antimalarial drug discovery [PubMed, https://pubmed.ncbi.nlm.nih.gov/32694768/]. Inhibition of PfGCN5 leads to widespread transcriptional dysregulation, resulting in the arrest of parasite growth and eventual death [PubMed, https://pubmed.ncbi.nlm.nih.gov/22493498/]. Current research focuses on identifying selective small-molecule inhibitors that target the HAT domain or the bromodomain to avoid cross-reactivity with human histone acetyltransferases [Scientific Reports, https://www.nature.com/articles/srep43532]. Such inhibitors represent a potential new class of therapeutics to combat multidrug-resistant malaria strains.

Other names

PfGCN5Histone acetyltransferase GCN5PF3D7_0823300GCN5-related N-acetyltransferase

Inhibition of the histone acetyltransferase (HAT) domain, preventing the acetylation of histone H3 lysine residues (H3K9 and H3K14) and disrupting the parasite's transcriptional program [PubMed, https://pubmed.ncbi.nlm.nih.gov/22493498/].