Structure based functional annotation of a MYND-less lysine methyl transferase inCandida albicans.

Abstract

Candida albicans is opportunistic pathogenic yeast that is widely distributed throughout the world and is classified as the most critical fungal pathogen group. Candida albicans is a common microbiota of healthy individuals but can cause superficial and invasive infections in immune compromised individuals. Protein Post-translational modifications involving methylation of lysine amino acids stand for a major regulator of eukaryotic transcription, and pathways controlling several cellular processes. SMYD makes up a SET (Su (Var) 3-9, Enhancer-of-zeste and Trithorax) and MYND (Myeloid, Nervy, and DEAF-1) domain containing lysine methyl transferase subfamily that transfers methyl groups from methyl donors onto lysine residues in histones (H3 and H4) and non-histone proteins. The SET domain is the methyltransferase catalytic domain, while MYND participates in both protein and DNA interactions. Well-studied examples of SMYD proteins are five human and two Saccharomyces cerevisiae, constituting examples of histone and non-histone protein lysine methyl transferase members. However, there is limited understanding of SET lysine methyltransferases, including the SMYD subfamily, in the pathogenic fungi Candida albicans. Using bioinformatics tools, we characterized the SMYD domain containing proteins in the important pathogen. We report the presence of an atypical SMYD member (CaO19.3863) as a new lysine methyltransferase that can be a target for antifungal therapy.