Crystal structure of HP0242, a hypothetical protein from Helicobacter pylori with a novel fold
Crystal structure of HP0242, a hypothetical protein from Helicobacter pylori with a novel fold
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DOI：
10.1002/prot.20864
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发表时间：
2006-03
期刊：
影响因子：
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通讯作者：
J. Tsai;Bo Chen;Hui-Chun Cheng;Hsin-Yi Chen;Nai-Wan Hsaio;P. Lyu;Yuh-Ju Sun
中科院分区：
文献类型：
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作者：
J. Tsai;Bo Chen;Hui-Chun Cheng;Hsin-Yi Chen;Nai-Wan Hsaio;P. Lyu;Yuh-Ju Sun
导论.幽门螺杆菌是一种螺旋形的革兰氏阴性微生物，于1979年发现，1982年分离。1994年，国际癌症研究机构宣布H。pylori是人类的致癌物。两个H. pylori 26695株和J 99株的全基因组随机序列测定结果表明，全基因组中约有33%的蛋白质序列被标注为“假想蛋白”，其功能和三维结构从未被确定。更好地了解这些蛋白质的细胞过程可以为发现潜在的抗菌药物靶标提供基础。因此，确定这些蛋白质的结构和功能关系，从而吸引了许多研究的关注。HP 0242是一种假设的由H. pylori菌株26695。基因组芯片分析表明，HP 0242是一个酸适应蛋白。提示HP 0242可能在细菌生理学中起重要作用。幽门螺杆菌在人胃的高酸性环境中定植。尽管HP 0242与其他功能蛋白没有显著的序列相似性，但用HP 0242进行的PSI-BLAST搜索显示了四种同源蛋白（图1）。HP 0242基因位于napA基因（HP 0243/HP-NAP）旁边，其上游含有铁摄取调节剂结合位点。该操纵子控制着7种蛋白质的协调表达。有五种功能蛋白（TIGR：http：//www.tigr.org/）：HP 0243（嗜中性粒细胞活化蛋白）、HP 0240（八异戊二烯基-二磷酸合酶）、HP 0239（谷氨酰-tRNA还原酶）、HP 0238（脯氨酰-tRNA合成酶）和HP 0237（胆色素原脱氨酶），以及两种假设蛋白HP 0242和HP 0241。已确定HP 0243、HP 0239和HP 0237的生物学功能与铁储存和血红素生物合成有关。我们通过对硒代甲硫氨酸（Se-HP 0242）蛋白进行多波长异常色散（MAD）定相，确定了HP 0242的三维结构。本文对HP 0242的新折叠结构进行了讨论，并从详细的结构分析中提出了可能的功能区域。
Introduction. Helicobacter pylori is a spiral-shaped, gram-negative microorganism that was found in 1979 and isolated in 1982. In 1994, the International Agency for Cancer Research declared H. pylori to be a carcinogen of human. Two complete genome sequences of H. pylori, strain 26695 and strain J99, have been determined by the whole-genome random sequencing method. About 33% protein sequences in the whole genome are annotated as “hypothetical proteins” whose functions and three-dimensional structures have never been identified. The better understanding of these proteins’ cellular processes could provide the basis for discoveries of potential antibacterial drug targets. Therefore, the determination of the structural and functional relationship of these proteins has thus drawn much research attention. HP0242 is a hypothetical protein encoded from H. pylori strain 26695. The genomic microarray analysis reveals that HP0242 is an acid-adaptive protein. It indicates that HP0242 may have an important function in bacteriological physiology when H. pylori colonize in the highly acidic environment of the human stomach. Although HP0242 has no significant sequence similarity with other functional proteins, a PSI-BLAST search with HP0242 shows four homology proteins (Fig. 1). The HP0242 gene is located next to the napA gene (HP0243/HP-NAP), which upstream contains a ferric-uptake regulator binding site. This operon governs coordinated expression of seven proteins totally. There are five functional proteins (TIGR: http://www.tigr.org/): HP0243 (neutrophil activating protein), HP0240 (octaprenyl-diphosphate synthase), HP0239 (glutamyl-tRNA reductase), HP0238 (prolyl-tRNA synthetase), and HP0237 (porphobilinogen deaminase), and two hypothetical proteins, HP0242 and HP0241. The biological functions of HP0243, HP0239, and HP0237 have been determined to be related to the iron storage and heme biosynthesis. We have determined the three-dimensional structure of HP0242 by multiwavelength anomalous dispersion (MAD) phasing from a selenomethinoine (Se-HP0242) protein. The novel folding of HP0242 will be discussed and the possible functional regions will be proposed from the detailed structure analysis.