摘要
目的应用生物信息学分析软件预测日本血吸虫乳酸脱氢酶(SjLDH)氨基酸序列的结构与功能。方法应用NCBI、Expasy等在线生物信息学网站及Vector NTI、PCgene等软件包分析SjLDH与其他物种的同源序列,进行多序列同源比对,分析相同的保守位点及催化活性位点,构建分子进化树;预测二级结构、拓扑结构;同源模建预测三级结构;预测主要抗原表位等。结果SjLDH与其他物种的同源序列含相同的保守位点及催化活性位点,与华支睾吸虫LDH(CsLDH)同源性最高为75%,与阴道毛滴虫LDH(TvLDH)同源性最低为17%,与人LDH(HsLDH-A,-B,-C)的同源性为58%～60%;SjLDH与果蝇(DmLDH)的进化距离较秀丽隐杆线虫(CeLDH)为近,3种人LDH中与HsLDH-B、-C的进化距离较HsLDH-A为近;该蛋白具有3个跨膜区域,3个高亲水性区域,主要的线性表位98aa￣106aa位于膜外,与原虫LDH相同区域差异显著,而与其他LDH有1～3个氨基酸的差异,关键催化位点之一及底物丙酮酸结合区域位于该区域,蛋白质同源模建分析表明该区域位于蛋白表面形成环状结构,3个关键催化位点位于该区域或在其附近。结论生物信息学预测结果提示LDH是研究物种分子进化理想的分子;SjLDH可能是免疫诊断、药物作用及疫苗潜在的靶分子。
Objective To predict the structure and function of SjLDH using bloinformatics method. Methods By online analysis at bioinformatics websites such as NCBI （http：//www.ncbi.nlm.nih.gov/） and Expasy （http：//cn,expasy. org/）, and employing software packages such as Vector NTI suite and PCgene to do multi-sequence homological alignment, phylogenetic analysis, secondary structure and topological prediction, homology modeling of tertiary structure, antigenic epitope analysis, etc. Results Same conservative sites and key catalytic sites existed among SjLDH and LDHs from other species. Similarity of SjLDH compared to CsLDH, TvLDH and HsLDH was 75%, 17%, 58%-60% respectively, Phylogenetic analysis demonstrated that the evolution relation between SjLDH and DmLDH was closer than the relation between SjLDH and CeLDH, the relationship between SjLDH and HsLDH-B, -C was closer than HsLDH-A. Three transmembrane regions were found, the region of 98aa-106aa in three hydrophilia regions located outside of membrane was inferred as the major antigen epitope, This antigen epitope had significant difference with LDHs from protozoon （Pf., Tg., Tv,） and had 1-3 amino acid residue difference with MmLDH, HsLDH-A, -B, -C, and was the same with CsLDH, One of the key catalytic residues and substrate （pyruvate） binding loop were located in this region. Tertiary structure demonstrated that 98aa-106aa was on the surface of the protein and formed a substrate binding loop, other two key catalytic sites were at the position near the loop. Conclusion The prediction implied that LDH was an ideal molecule for phylogenetic analysis; SjLDH might be a potential molecular target for immunodiagnosis, anti-schistosome drug and vaccine development.
出处
《中国寄生虫学与寄生虫病杂志》
CAS
CSCD
北大核心
2007年第3期202-205,共4页
Chinese Journal of Parasitology and Parasitic Diseases
基金
国家自然科学基金(No.30571633)~~
关键词
日本血吸虫
乳酸脱氢酶
生物信息学
结构
功能
Schistosoma japonicum
Lactate dehydrogenase
Bioinforrnatics
Structure
Function
