Leishmania 18S ribosomal RNA helix 44 (h44)

Helix 44 (h44) of the 18S ribosomal RNA (rRNA) is a fundamental structural component of the small ribosomal subunit (40S) in Leishmania species, serving as the core of the ribosomal decoding center or A-site [1, 3]. Its primary biological function is to ensure the fidelity of translation by facilitating the correct pairing between mRNA codons and tRNA anticodons [10, 14]. This helix is the specific molecular target for aminoglycoside antibiotics, most notably paromomycin, which binds to the major groove of the RNA [3, 6]. The binding of paromomycin to h44 induces a conformational change that mimics the state of correct codon-anticodon recognition, leading to the incorporation of incorrect amino acids (mistranslation) and subsequent inhibition of protein synthesis [1, 6]. While h44 is highly conserved, subtle sequence differences between the Leishmania decoding site and the human cytosolic or mitochondrial counterparts allow for selective toxicity, making it a validated therapeutic target for both cutaneous and visceral leishmaniasis [1, 3, 12].

Other names

18S rRNA helix 44Ribosomal decoding siteA-siteSmall subunit ribosomal RNA helix 44

Inhibition of protein synthesis by binding to the decoding A-site (helix 44), inducing mRNA mistranslation and preventing ribosomal translocation [1, 6, 10].