曼氏血吸虫己糖激酶（SmHK）蛋白质结构与功能的生物信息学预测

目的应用生物信息学技术预测曼氏血吸虫己糖激酶（SmHK）的结构和功能，为进一步功能研究提供信息。方法从GenBank获取SmHK及其他物种HK全长eDNA序列及氨基酸序列，应用NCBI、Expasy等在线生物信息学网站及VectorNTI软件包，对所获氨基酸序列的保守功能域及基序、蛋白质理化参数、亚细胞定位、亲水性、B细胞线性表位、二级结构及拓扑结构、三级结构建模分析及预测。结果SmHK编码451氨基酸残基，理论分子量为50446．01Da，具有完整HK-1及HK-2保守功能域，与结构和功能有关的位点高度保守，与宿主（人、鼠）的同源性为30％，与人等脊椎动物有较近的进化关系；有多个潜在的抗原表位、多个磷酸化位点及1个跨膜结构。三级结构分子建模显示该蛋白两基团间有一裂隙，葡萄糖、ATP结合位点及ATP催化区位于该裂隙中或周围，跨膜区与其两端的碱性氨基酸形成一阴离子通道。结论SmHK与结构和功能相关的位点高度保守。与宿主有较近的进化关系，推测该蛋白可能通过跨膜区锚定在线粒体外膜上，主要功能位点位于蛋白裂隙中或周围，多个磷酸化位点说明其参与多种细胞功能的调节，在调节能量代谢中起重要作用，是潜在的疫苗候选分子和药物作用靶标。

Bioinformatics Prediction of the Structure and Function of Hexokinase from Schistosoma mansoni

Objective To predict the structure and function of hexokinase from Schistosoma mansoni （SmHK） using bioinformatics. Methods Complete cDNA sequences and the deduced amino acid sequences of hexokinase from S. mansoni and other species were obtained from GenBank. The bioinformatics websites such as NCBI, Expasy and the software package such as Vector NTI were used to predict the conserved domain and motif, multi-sequence homological alignment, phylogenetic analysis, protein parameters, subcellular localization, hydrophihcity and B-cell linear epitope, secondary and topological structure, and homology modeling of tertiary structure. Results SmHK was found to have 451 amino acid residues, and the predicted molecular weight was 50 446.01 Da. The conserved domains were found in the HK-1 and HK-2. It had the same conserved amino acid residues as HKs from other species. Most of the HKs had the same conserved structural and functional domain. SmHK shared 30% homology with HKs from other hosts （Homo sapiens, Mus musculus）. Phylogenetic analysis showed that the evolutionary relationship between SmHK and HKs from vertebrates was closer than that of invertebrates. Several potential antigenic epitopes, phosphorylation sites and other sites were found in the sequence. One potential transmembrane region was also identified. The three-dimensional model of SmHK showed that there were glucose bind sites, ATP bind sites as well as ATP catalytic regions located in or near the cleft. The transmembrane region and the two basic amino acids at both N- and C- end of this region formed an anion channel. Conclusion Valuable information about SmHK was obtained by bioinformatics. The constructed functional sites are highly conserved. Phylogenetic analysis showed it had a closer evolutionary relationship with HK from vertebrates than invertebrates. The protein is presumably anchored at outer membrane of mitochondria through the transmembrane region. The functional sites are located in or near the cleft of the protein. The presence of multiple phosphorylation sites suggested that SmHK may be involved in the regulation of various cellular functions. It may play an important role in energy metabolism of the parasites. It might be a potential molecular target for the development of vaccines and drugs against the schistosomes.