Dicyclomine is a selective muscarinic M1 receptor antagonist in humans. Dicyclomine targets signal transduction genes and inhibits virulence factors in the human pathogen, Candida albicans. Muscarinic acetylcholine receptors are not known to exist in C. albicans. We carried out a search to identify a muscarinic receptor like proteins in C. albicans. A BLAST protein analysis revealed that a C. albicans protein Rrp9 shares 54% identity and 71% similarity with human muscarinic M1 receptor at 24 amino acids overlap. Global alignment between human muscarinic M1 receptor and C. albicans Rrp9 showed 19% identity and 33% similarity at 570 amino acid residues overlap. Our molecular docking study of dicyclomine with C. albicans, Rrp9, Gpr1, Ste2 and Ste3 showed that dicyclomine could bind only with Rrp9 by forming hydrogen bond interactions with VAL386 and ILE313 amino acid residues in the active site region. Dicyclomine bound with human muscarinic receptor M1 by forming hydrogen bond interaction with ARG123 at the active site region. Our study suggests that Rrp9 may be considered as a potential target for dicyclomine in C. albicans.
Awad Ali, Archana Wakharde and Sankunny Mohan Karuppayil
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