申克孢子丝菌Sec14基因相关功能和药物靶点分析  

Functional and drug target analysis of Sec14 gene in Sporothrix schenckii

作　　者：吴晓雁 张静[2] 高文超[1] 李玉哲[3] 吴榕 陈三妹 黄怀球[1] WU Xiao-yan;ZHANG Jing;GAO Wen-chao;LI Yu-zhe;WU Rong;CHEN San-mei;HUANG Huai-qiu(Department of Dermatology and Venereology,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510630;Department of Dermatology,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510120;Department of Clinical Laboratory,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510630;Department of General Practice,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510630,China)

机构地区：[1]中山大学附属第三医院皮肤性病科,广东广州510630 [2]中山大学孙逸仙纪念医院皮肤科,广东广州510120 [3]中山大学附属第三医院检验科,广东广州510630 [4]中山大学附属第三医院全科医学,广东广州510630

出　　处：《热带医学杂志》2020年第4期436-440,F0002,共6页Journal of Tropical Medicine

基　　金：国家自然科学基金(81974300,81371746);广东省科技厅社会公益性研究项目(2016A020215066);中山大学三大建设超算专项(82000-31143405)。

摘　　要：目的初步了解申克孢子丝菌Sec14基因DNA、m RNA、蛋白的生物学特征及功能位点。方法生物信息学方法分析申克孢子丝菌Sec14基因DNA、m RNA、蛋白的生物学特征。结果申克孢子丝菌Sec14基因启动子可能位于其基因编码区起始位点前224~274 bp处,包含转录起始位点-265 bp,该基因无内含子;Sec14 mRNA含有丰富转录调节元件,并含有microRNA结合位点;Sec14p样蛋白由351个氨基酸残基构成,分子量为39×10^3Mr,理论等电点为5.25,二级结构主要由α-螺旋和无规卷曲构成,Sec14p样蛋白的三级结构呈现典型的球状结构,包裹一个疏水性口袋,该区域含有磷脂分子结合区域,蛋白还分布着丰富的磷酸化位点及2个二分裂核定位信号。吡啶酰胺小分子化合物在磷脂分子结合区域与蛋白相作用,结合能为-6.5 kcal/mol,蛋白还具有丰富的抗原表位。Sec14p样蛋白序列在大部分真菌中一致性较好,同源性高。结论申克孢子丝菌Sec14基因具有典型真菌基因组基因特征,mRNA可变性高,其编码蛋白的磷脂分子结合位点可作为新型小分子的药物靶点。Objective To understand the biological characteristics and functions of DNA,mRNA and protein of Sporothrix schenckii Sec14 gene. Methods Bioinformatic analysis softwares were utilized to analyze biological characteristics of DNA,mRNA and protein of Sporothrix shcenckii Sec14 gene. Results The promoter of Sec14 gene from Sporothrix schenckii may be located 224-274 bp before the start site of its coding region,containing the transcription start site,-265 bp. Sec14 gene has no intron. Sec14 mRNA contains abundant transcriptional regulatory elements as well as two microRNA binding sites;Sec14-like protein is composed of 351 amino acid residues,with a molecular weight of 39×10^3 Mr,with a theoretical isoelectric point of 5.25. The protein consists of abundant α-helix and random coil to form a typical globular structure,wrapping a hydrophobic pocket. In addition to the binding region for phospholipid molecule in the pocket,the protein also contains multiple phosphorylation sites and two bipartite nuclear localization signals. The pyridinamide small molecule compound binds to the protein in the phospholipid molecule binding region with a binding energy of-6.5 kcal/mol,and the protein also contains abundant antigenic epitopes. The Sec14-like protein sequence is well-aligned and highly homologous in most of the fungi. Conclusions The Sporothrix schenckii Sec14 gene is a typical fungal genomic gene, and the mRNA is highly variable.The phospholipid molecule binding site of Sec14-like protein may be an ideal target for novel small molecule drug.

关 键 词：申克孢子丝菌 生物信息学分析 Sec14基因 吡啶酰胺 

分 类 号：R378[医药卫生—病原生物学]