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.
摘要:
白色念珠菌是一种广泛分布于世界各地的机会致病性酵母,被列为最关键的真菌病原体组。白色念珠菌是健康个体的常见微生物群,但可在免疫受损的个体中引起表面和侵入性感染。涉及赖氨酸氨基酸甲基化的蛋白质翻译后修饰是真核转录的主要调节因子,和控制几个细胞过程的途径。SMYD组成SET(Su(Var)3-9,zeste和Trithorax增强剂)和MYND(髓系,紧张,和DEAF-1)包含赖氨酸甲基转移酶亚家族的结构域,将甲基从甲基供体转移到组蛋白(H3和H4)和非组蛋白蛋白中的赖氨酸残基上。SET结构域是甲基转移酶催化结构域,而MYND参与蛋白质和DNA的相互作用。SMYD蛋白的研究良好的例子是五个人和两个酿酒酵母,构成组蛋白和非组蛋白赖氨酸甲基转移酶成员的例子。然而,对SET赖氨酸甲基转移酶的了解有限,包括SMYD亚家族,在病原真菌白色念珠菌中。使用生物信息学工具,我们表征了重要病原体中含有SMYD结构域的蛋白质。我们报告了非典型SMYD成员(CaO19.3863)作为一种新的赖氨酸甲基转移酶的存在,可以成为抗真菌治疗的靶标。