Crystal structure of HP02429, a hypothetical protein from Helicobaccter pylori wrath a novel fold

[[abstract]]Helicobacter pylori is a spiral-shaped, gram-negative microorganism that was found in 1979 and isolated in 1982.1 In 1994, the International Agency for Cancer Research declared H. pylori to be a carcinogen of human.2 Two complete genome sequences of H. pylori, strain 26695 and strain J99, have been determined by the whole-genome random sequencing method.3,4 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.5 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),3 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 HP0243,6,7 HP0239,3 and HP02373 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.[[fileno]]2050134010031[[department]]生科