{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:25:48Z","timestamp":1782278748412,"version":"3.54.5"},"reference-count":123,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2012,6,8]],"date-time":"2012-06-08T00:00:00Z","timestamp":1339113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Helicobacter pylori (H. pylori) have a unique ability to survive in extreme acidic environments and to colonize the gastric mucosa. It can cause diverse gastric diseases such as peptic ulcers, chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, gastric cancer, etc. Based on genomic research of H. pylori, over 1600 genes have been functionally identified so far. However, H. pylori possess some genes that are uncharacterized since: (i) the gene sequences are quite new; (ii) the function of genes have not been characterized in any other bacterial systems; and (iii) sometimes, the protein that is classified into a known protein based on the sequence homology shows some functional ambiguity, which raises questions about the function of the protein produced in H. pylori. Thus, there are still a lot of genes to be biologically or biochemically characterized to understand the whole picture of gene functions in the bacteria. In this regard, knowledge on the 3D structure of a protein, especially unknown or hypothetical protein, is frequently useful to elucidate the structure-function relationship of the uncharacterized gene product. That is, a structural comparison with known proteins provides valuable information to help predict the cellular functions of hypothetical proteins. Here, we show the 3D structures of some hypothetical proteins determined by NMR spectroscopy and X-ray crystallography as a part of the structural genomics of H. pylori. In addition, we show some successful approaches of elucidating the function of unknown proteins based on their structural information.<\/jats:p>","DOI":"10.3390\/ijms13067109","type":"journal-article","created":{"date-parts":[[2012,6,8]],"date-time":"2012-06-08T11:25:11Z","timestamp":1339154711000},"page":"7109-7137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Structural Analysis of Hypothetical Proteins from Helicobacter pylori: An Approach to Estimate Functions of Unknown or Hypothetical Proteins"],"prefix":"10.3390","volume":"13","author":[{"given":"Sung Jean","family":"Park","sequence":"first","affiliation":[{"name":"College of Pharmacy, Gachon University, 534-2 Yeonsu 3-dong, Yeonsu-gu, Incheon 406-799, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Sung","family":"Son","sequence":"additional","affiliation":[{"name":"College of Pharmacy, CHA University, 120 Haeryong-ro, Pocheon-si, Gyeonggi-do 487-010, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2012,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/S1286-4579(03)00111-4","article-title":"Burden of Helicobacter pylori and H. pylori-related diseases in developed countries: Recent developments and future implications","volume":"5","author":"Rothenbacher","year":"2003","journal-title":"Microbes Infect"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/0140-6736(93)91409-F","article-title":"Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori","volume":"342","author":"Wotherspoon","year":"1993","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nrc703","article-title":"Helicobacter pylori and gastrointestinal tract adenocarcinomas","volume":"2","author":"Peek","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1056\/NEJM199110173251603","article-title":"Helicobacter pylori infection and the risk of gastric carcinoma","volume":"325","author":"Parsonnet","year":"1991","journal-title":"N. Engl. J. Med"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1523-5378.2008.00633.x","article-title":"Helicobacter and gastric malignancies","volume":"13","author":"Ferreira","year":"2008","journal-title":"Helicobacter"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nrgastro.2010.154","article-title":"Mechanisms of disease: Helicobacter pylori virulence factors","volume":"7","author":"Yamaoka","year":"2010","journal-title":"Nat. Rev. Gastroenterol. Hepatol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.bpg.2006.04.006","article-title":"Role of host genes in sporadic gastric cancer","volume":"20","year":"2006","journal-title":"Best Pract. Res. Clin. Gastroenterol"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1016\/S0016-5085(97)70019-2","article-title":"Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: A model","volume":"113","author":"Graham","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1751-2980.2009.00368.x","article-title":"African, Asian or Indian enigma, the East Asian Helicobacter pylori: Facts or medical myths","volume":"10","author":"Graham","year":"2009","journal-title":"J. Dig. Dis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2008.11.016","article-title":"Helicobacter pylori virulence factors in gastric carcinogenesis","volume":"282","author":"Wen","year":"2009","journal-title":"Cancer Lett"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1172\/JCI20925","article-title":"Helicobacter pylori persistence: Biology and disease","volume":"113","author":"Blaser","year":"2004","journal-title":"J. Clin. Invest"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1126\/science.1069076","article-title":"Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation","volume":"297","author":"Mahdavi","year":"2002","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1053\/j.gastro.2005.01.009","article-title":"Duodenal ulcer promoting gene of Helicobacter pylori","volume":"128","author":"Lu","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1523-5378.2011.00876.x","article-title":"Pathogenesis of Helicobacter pylori infection","volume":"1","author":"Backert","year":"2011","journal-title":"Helicobacter"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/41483","article-title":"The complete genome sequence of the gastric pathogen Helicobacter pylori","volume":"388","author":"Tomb","year":"1997","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/16495","article-title":"Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori","volume":"397","author":"Alm","year":"1997","journal-title":"Nature"},{"key":"ref_17","unstructured":"Available online: http:\/\/www.ncbi.nlm.nih.gov\/genome."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0168-9525(90)90254-4","article-title":"The genetics of protein secretion in E. coli","volume":"6","author":"Bieker","year":"1990","journal-title":"Trends Genet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1128\/JB.184.10.2837-2840.2002","article-title":"The secE gene of Helicobacter pylori","volume":"184","author":"Medigue","year":"2002","journal-title":"J. Bacteriol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1101\/gad.901001","article-title":"Identification of novel small RNAs using comparative genomics and microarrays","volume":"15","author":"Wassarman","year":"2001","journal-title":"Genes Dev"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10482-007-9152-8","article-title":"Identification and characterisation of ssrA in members of the Helicobacter genus","volume":"92","author":"Dong","year":"2007","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrmicro1491","article-title":"Bacterial RNase P: A new view of an ancient enzyme","volume":"4","author":"Kazantsev","year":"2006","journal-title":"Nat. Rev. Microbiol"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6435","DOI":"10.1093\/nar\/gkg867","article-title":"RNomics in Escherichia coli detects new sRNA species and indicates parallel transcriptional output in bacteria","volume":"31","author":"Vogel","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.1073\/pnas.0800668105","article-title":"Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells","volume":"105","author":"Giannakis","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Raymond, J., Thiberge, J.M., Kalach, N., Bergeret, M., Dupont, C., Labigne, A., and Dauga, C. (2008). Using macro-arrays to study routes of infection of Helicobacter pylori in three families. PLoS One, 3.","DOI":"10.1371\/journal.pone.0002259"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1128\/JB.01416-08","article-title":"The complete genome sequence of Helicobacter pylori strain G27","volume":"191","author":"Baltrus","year":"2009","journal-title":"J. Bacteriol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.1073\/pnas.90.12.5791","article-title":"Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer","volume":"90","author":"Covacci","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9999","DOI":"10.1073\/pnas.0603784103","article-title":"The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: Evolution during disease progression","volume":"103","author":"Oh","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"McClain, M.S., Shaffer, C.L., Israel, D.A., Peek, R.M., and Cover, T.L. (2009). Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer. BMC Genomics, 10.","DOI":"10.1186\/1471-2164-10-3"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6488","DOI":"10.1128\/JB.01110-10","article-title":"Genome of Helicobacter pylori strain 908","volume":"192","author":"Devi","year":"2010","journal-title":"J. Bacteriol"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Farnbacher, M., Jahns, T., Willrodt, D., Daniel, R., Haas, R., Goesmann, A., Kurtz, S., and Rieder, G. (2010). Sequencing, annotation, and comparative genome analysis of the gerbil-adapted Helicobacter pylori strain B8. BMC Genomics, 11.","DOI":"10.1186\/1471-2164-11-335"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6089","DOI":"10.1093\/nar\/gkq378","article-title":"Strain-specific genes of Helicobacter pylori: Genome evolution driven by a novel type IV secretion system and genomic island transfer","volume":"38","author":"Fischer","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kersulyte, D., Kalia, A., Gilman, R.H., Mendez, M., Herrera, P., Cabrera, L., Velapatino, B., Balqui, J., Paredes Puente de la Vega, F., and Rodriguez Ulloa, C.A. (2010). Helicobacter pylori from Peruvian amerindians: Traces of human migrations in strains from remote Amazon, and genome sequence of an Amerind strain. PLoS One, 5.","DOI":"10.1371\/journal.pone.0015076"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1128\/JB.00063-10","article-title":"Host-interactive genes in Amerindian Helicobacter pylori diverge from their Old World homologs and mediate inflammatory responses","volume":"192","author":"Mane","year":"2010","journal-title":"J. Bacteriol"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Thiberge, J.M., Boursaux-Eude, C., Lehours, P., Dillies, M.A., Creno, S., Coppee, J.Y., Rouy, Z., Lajus, A., Ma, L., and Burucoa, C. (2010). From array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma. BMC Genomics, 11.","DOI":"10.1186\/1471-2164-11-368"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3385","DOI":"10.1128\/JB.05006-11","article-title":"Genomes of two chronological isolates (Helicobacter pylori 2017 and 2018) of the West African Helicobacter pylori strain 908 obtained from a single patient","volume":"193","author":"Avasthi","year":"2011","journal-title":"J. Bacteriol"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1073\/pnas.1012579108","article-title":"Birth and death of genes linked to chromosomal inversion","volume":"108","author":"Furuta","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lehours, P., Vale, F.F., Bjursell, M.K., Melefors, O., Advani, R., Glavas, S., Guegueniat, J., Gontier, E., Lacomme, S., and Alves Matos, A. (2011). Genome sequencing reveals a phage in Helicobacter pylori. MBio, 2.","DOI":"10.1128\/mBio.00239-11"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1128\/JCM.01631-07","article-title":"Microevolution of Helicobacter pylori type IV secretion systems in an ulcer disease patient over a ten-year period","volume":"45","author":"Alvi","year":"2007","journal-title":"J. Clin. Microbiol"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1128\/JCM.43.8.4237-4241.2005","article-title":"Pathogen evolution in vivo: Genome dynamics of two isolates obtained 9 years apart from a duodenal ulcer patient infected with a single Helicobacter pylori strain","volume":"43","author":"Hussain","year":"2005","journal-title":"J. Clin. Microbiol"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/nature05562","article-title":"An African origin for the intimate association between humans and Helicobacter pylori","volume":"445","author":"Linz","year":"2007","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Falush, D., Wirth, T., Linz, B., Pritchard, J.K., Stephens, M., Kidd, M., Blaser, M.J., Graham, D.Y., Vacher, S., and Perez-Perez, G.I. (2003). Science, 299, 1582\u20131585.","DOI":"10.1126\/science.1080857"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.1073\/pnas.0306629101","article-title":"Distinguishing human ethnic groups by means of sequences from Helicobacter pylori: Lessons from Ladakh","volume":"101","author":"Wirth","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/nar\/29.1.123","article-title":"The comprehensive microbial resource","volume":"29","author":"Peterson","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1128\/MMBR.63.3.642-674.1999","article-title":"Metabolism and genetics of Helicobacter pylori: The genome era","volume":"63","author":"Marais","year":"1999","journal-title":"Microbiol. Mol. Biol. Rev"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6510","DOI":"10.1128\/IAI.71.11.6510-6525.2003","article-title":"Growth phase-dependent response of Helicobacter pylori to iron starvation","volume":"71","author":"Merrell","year":"2003","journal-title":"Infect. Immun"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5921","DOI":"10.1128\/IAI.71.10.5921-5939.2003","article-title":"Acid-adaptive genes of Helicobacter pylori","volume":"71","author":"Wen","year":"2003","journal-title":"Infect. Immun"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1021\/cb900166q","article-title":"Discovery of specific flavodoxin inhibitors as potential therapeutic agents against Helicobacter pylori infection","volume":"4","author":"Cremades","year":"2009","journal-title":"ACS Chem. Biol"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4842","DOI":"10.1074\/jbc.M109.097840","article-title":"Functional identification of toxin-antitoxin molecules from Helicobacter pylori 26695 and structural elucidation of the molecular interactions","volume":"286","author":"Han","year":"2011","journal-title":"J. Biol. Chem"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1002\/prot.20691","article-title":"Solution structure of conserved hypothetical protein HP0894 from Helicobacter pylori","volume":"61","author":"Han","year":"2005","journal-title":"Proteins"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/S1097-2765(00)00142-8","article-title":"Crystal structure of the hexameric traffic ATPase of the Helicobacter pylori type IV secretion system","volume":"6","author":"Yeo","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_52","unstructured":"Available online: http:\/\/www.rcsb.org."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S1047-8477(03)00044-3","article-title":"Protein production in Escherichia coli for structural studies by X-ray crystallography","volume":"142","author":"Goulding","year":"2003","journal-title":"J. Struct. Biol"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1128\/jb.174.8.2466-2473.1992","article-title":"Expression of Helicobacter pylori urease genes in Escherichia coli grown under nitrogen-limiting conditions","volume":"174","author":"Cussac","year":"1992","journal-title":"J. Bacteriol"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.2174\/092986608786071085","article-title":"Function prediction of hypothetical proteins without sequence similarity to proteins of known function","volume":"15","author":"Kannan","year":"2008","journal-title":"Protein Pept. Lett"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nprot.2007.494","article-title":"Cell-PLoc: A package of Web servers for predicting subcellular localization of proteins in various organisms","volume":"3","author":"Chou","year":"2008","journal-title":"Nat. Protoc"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbrc.2007.09.098","article-title":"EzyPred: A top-down approach for predicting enzyme functional classes and subclasses","volume":"364","author":"Shen","year":"2007","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.2174\/0929867043364702","article-title":"Doig, A.J. Prediction of protein function in the absence of significant sequence similarity","volume":"11","author":"Dobson","year":"2004","journal-title":"Curr. Med. Chem"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"W116","DOI":"10.1093\/nar\/gkl282","article-title":"CASTp: Computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues","volume":"34","author":"Dundas","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1093\/bioinformatics\/btn507","article-title":"Searching protein structure databases with DaliLite v.3","volume":"24","author":"Holm","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"W545","DOI":"10.1093\/nar\/gkq366","article-title":"Dali server: Conservation mapping in 3D","volume":"38","author":"Holm","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/1097-0134(20001001)41:1<108::AID-PROT130>3.0.CO;2-S","article-title":"Protein structure comparison using the markov transition model of evolution","volume":"41","author":"Kawabata","year":"2000","journal-title":"Proteins"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.str.2008.10.017","article-title":"Detection of functionally important regions in \u201chypothetical proteins\u201d of known structure","volume":"16","author":"Nimrod","year":"2008","journal-title":"Structure"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1006\/jmbi.2001.4870","article-title":"Automated structure-based prediction of functional sites in proteins: Applications to assessing the validity of inheriting protein function from homology in genome annotation and to protein docking","volume":"311","author":"Aloy","year":"2001","journal-title":"J. Mol. Biol"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12473","DOI":"10.1073\/pnas.211436698","article-title":"THEMATICS: A simple computational predictor of enzyme function from structure","volume":"98","author":"Ondrechen","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"14754","DOI":"10.1073\/pnas.0404569101","article-title":"Automated prediction of protein function and detection of functional sites from structure","volume":"101","author":"Pazos","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jmb.2007.03.036","article-title":"HotPatch: A statistical approach to finding biologically relevant features on protein surfaces","volume":"369","author":"Pettit","year":"2007","journal-title":"J. Mol. Biol"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1110\/ps.03328504","article-title":"Sensitivity and selectivity in protein structure comparison","volume":"13","author":"Sierk","year":"2004","journal-title":"Protein Sci"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0076-6879(96)66029-7","article-title":"Local alignment statistics","volume":"266","author":"Altschul","year":"1996","journal-title":"Methods Enzymol"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/prot.20691","article-title":"Solution structure of conserved hypothetical protein HP0894 from Helicobacter pylori","volume":"61","author":"Han","year":"2005","journal-title":"Proteins"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"W327","DOI":"10.1093\/nar\/gkh454","article-title":"CD-Search: Protein domain annotations on the fly","volume":"32","author":"Bryant","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/nar\/30.1.276","article-title":"The Pfam protein families data base","volume":"30","author":"Bateman","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nsmb911","article-title":"Crystal structure of archaeal toxin-antitoxin RelE-RelB complex with implications for toxin activity and antitoxin effects","volume":"12","author":"Takagi","year":"2005","journal-title":"Nat. Struct. Mol. Biol"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrmicro1147","article-title":"Prokaryotic toxin-antitoxin stress response loci","volume":"3","author":"Gerdes","year":"2005","journal-title":"Nat. Rev. Microbiol"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nsmb0405-282","article-title":"RelBE or not to be","volume":"12","author":"Wilson","year":"2005","journal-title":"Nat. Struct. Mol. Biol"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4842","DOI":"10.1074\/jbc.M109.097840","article-title":"Functional identification of toxin-antitoxin molecules from Helicobacter pylori 26695 and structural elucidation of the molecular interactions","volume":"286","author":"Han","year":"2011","journal-title":"J. Biol. Chem"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S1097-2765(03)00097-2","article-title":"Crystal structure of the MazE\/MazF complex: Molecular bases of antidote-toxin recognition","volume":"11","author":"Kamada","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/prot.21701","article-title":"Solution structure of conserved hypothetical protein HP0892 from Helicobacter pylori","volume":"70","author":"Han","year":"2008","journal-title":"Proteins"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1128\/IAI.73.6.3794-3798.2005","article-title":"Genomic comparison of cag pathogenicity island (PAI)-positive and -negative Helicobacter pylori strains: Identification of novel markers for cag PAI-positive strains","volume":"73","author":"Terry","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0378-1119(95)00315-W","article-title":"Identification of a gene encoding a bacteriophage-related integrase in a vap region of the Dichelobacter nodosus genome","volume":"162","author":"Cheetham","year":"1995","journal-title":"Gene"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.1128\/iai.60.11.4586-4592.1992","article-title":"Molecular characterization of a genomic region associated with virulence in Dichelobacter nodosus","volume":"60","author":"Katz","year":"1992","journal-title":"Infect. Immun"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6840","DOI":"10.1128\/IAI.68.12.6840-6847.2000","article-title":"DNA sequence and comparison of virulence plasmids from Rhodococcus equi ATCC 33701 and 103","volume":"68","author":"Takai","year":"2000","journal-title":"Infect. Immun"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/41483","article-title":"The complete genome sequence of the gastric pathogen Helicobacter pylori","volume":"388","author":"Tomb","year":"1997","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.1128\/iai.60.11.4586-4592.1992","article-title":"Molecular characterization of a genomic region associated with virulence in Dichelobacter nodosus","volume":"60","author":"Katz","year":"1992","journal-title":"Infect. Immun"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0923-2508(01)01217-7","article-title":"Induction of vap genes encoded by the virulence plasmid of Rhodococcus equi during acid tolerance response","volume":"152","author":"Benoit","year":"2001","journal-title":"Res. Microbiol"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1006\/plas.1994.1016","article-title":"Characterization of pVT736-1, a rolling-circle plasmid from the gram-negative bacterium Actinobacillus actinomycetemcomitans","volume":"31","author":"Galli","year":"1994","journal-title":"Plasmid"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4216","DOI":"10.1093\/nar\/gkr1305","article-title":"Structural and biochemical characterization of HP0315 from Helicobacter pylori as a VapD protein with an endoribonuclease activity","volume":"40","author":"Kwon","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Makarova, K.S., Grishin, N.V., Shabalina, S.A., Wolf, Y.I., and Koonin, E.V. (2006). A putative RNA-interference-based immune system in prokaryotes: Computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol. Direct, 1.","DOI":"10.1186\/1745-6150-1-7"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/jb\/mvp098","article-title":"Crystal structure of hypothetical protein HP0062 (O24902_HELPY) from Helicobacter pylori at 1.65 A resolution","volume":"146","author":"Jang","year":"2009","journal-title":"J. Biochem"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0966-842X(02)02345-4","article-title":"The ESAT-6\/WXG100 superfamily\u2014And a new Gram-positive secretion system?","volume":"10","author":"Pallen","year":"2002","journal-title":"Trends Microbiol"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1046\/j.1365-2958.2001.02354.x","article-title":"Type III export: New uses for an old pathway","volume":"40","author":"Plano","year":"2001","journal-title":"Mol. Microbiol"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1002\/prot.21346","article-title":"Solution structure of hypothetical protein, HP0495 (Y495_HELPY) from Helicobacter pylori","volume":"67","author":"Seo","year":"2007","journal-title":"Proteins"},{"key":"ref_95","first-page":"839","article-title":"Backbone 1H, 15N, and 13C resonance assignment and secondary structure prediction of HP0495 from Helicobacter pylori","volume":"40","author":"Seo","year":"2007","journal-title":"J. Biochem. Mol. Biol"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1093\/jb\/mvp105","article-title":"NMR solution structure of HP0827 (O25501_HELPY) from Helicobacter pylori: Model of the possible RNA-binding site","volume":"146","author":"Jang","year":"2009","journal-title":"J. Biochem"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/nar\/30.1.276","article-title":"The Pfam protein families database","volume":"30","author":"Bateman","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"ref_98","first-page":"591","article-title":"Backbone 1H, 15N, and 13C resonance assignment of HP1242 from Helicobacter pylori","volume":"38","author":"Kang","year":"2005","journal-title":"J. Biochem. Mol. Biol"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/prot.20654","article-title":"Solution structure of HP1242 from Helicobacter pylori","volume":"61","author":"Kang","year":"2005","journal-title":"Proteins"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/PL00006472","article-title":"Novel predicted RNA-binding domains associated with the translation machinery","volume":"48","author":"Aravind","year":"1999","journal-title":"J. Mol. Evol"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/prot.22335","article-title":"Solution structure of hypothetical protein HP1423 (Y1423_HELPY) reveals the presence of alphaL motif related to RNA binding","volume":"75","author":"Kim","year":"2009","journal-title":"Proteins"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1367-5931(03)00032-2","article-title":"Enzymes with extra talents: Moonlighting functions and catalytic promiscuity","volume":"7","author":"Copley","year":"2003","journal-title":"Curr. Opin. Chem. Biol"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"12775","DOI":"10.1016\/S0021-9258(18)31455-8","article-title":"Primary structure of two P-type ATPases involved in copper homeostasis in Enterococcus hirae","volume":"268","author":"Odermatt","year":"1993","journal-title":"J. Biol. Chem"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1074\/jbc.270.9.4349","article-title":"Two trans-acting metalloregulatory proteins controlling expression of the copper-ATPases of Enterococcus hirae","volume":"270","author":"Odermatt","year":"1995","journal-title":"J. Biol. Chem"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1006\/bbrc.1999.0807","article-title":"Effects of promoter mutations on the in vivo regulation of the cop operon of Enterococcus hirae by copper(I) and copper(II)","volume":"259","author":"Solioz","year":"1999","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1126\/science.278.5339.853","article-title":"Metal ion chaperone function of the soluble Cu(I) receptor Atx1","volume":"278","author":"Pufahl","year":"1997","journal-title":"Science"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1021\/bi027096p","article-title":"Understanding copper trafficking in bacteria: Interaction between the copper transport protein CopZ and the N-terminal domain of the copper ATPase CopA from Bacillus subtilis","volume":"42","author":"Banci","year":"2003","journal-title":"Biochemistry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4676","DOI":"10.1128\/jb.179.15.4676-4683.1997","article-title":"Identification and characterization of an operon of Helicobacter pylori that is involved in motility and stress adaptation","volume":"179","author":"Beier","year":"1997","journal-title":"J. Bacteriol"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1128\/JB.180.2.317-329.1998","article-title":"Properties of the P-type ATPases encoded by the copAP operons of Helicobacter pylori and Helicobacter felis","volume":"180","author":"Bayle","year":"1998","journal-title":"J. Bacteriol"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0168-6445(03)00053-6","article-title":"Copper homeostasis in Enterococcus hirae","volume":"27","author":"Solioz","year":"2003","journal-title":"FEMS Microbiol. Rev"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/prot.21957","article-title":"Structural insight into the distinct properties of copper transport by the Helicobacter pylori CopP protein","volume":"71","author":"Park","year":"2008","journal-title":"Proteins"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev.mi.43.100189.001533","article-title":"Genetics and regulation of bacterial lipid metabolism","volume":"43","author":"Vandem","year":"1989","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1021\/bi00386a037","article-title":"Structural comparison of acyl carrier protein in acylated and sulfhydryl forms by two-dimensional 1H NMR spectroscopy","volume":"26","author":"Jones","year":"1987","journal-title":"Biochemistry"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1016\/S0021-9258(18)34627-1","article-title":"Molecular properties of short chain acyl thioesters of acyl carrier protein","volume":"257","author":"Cronan","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/jb\/mvh041","article-title":"pH-induced conformational transition of H. pylori acyl carrier protein: Insight into the unfolding of local structure","volume":"135","author":"Park","year":"2004","journal-title":"J. Biochem"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0021-9258(19)41715-8","article-title":"On the structure-function relationship of acyl carrier protein of Escherichia coli","volume":"250","author":"Schulz","year":"1975","journal-title":"J. Biol. Chem"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"35934","DOI":"10.1074\/jbc.M101849200","article-title":"Site-directed mutagenesis of acyl carrier protein (ACP) reveals amino acid residues involved in ACP structure and acyl-ACP synthetase activity","volume":"276","author":"Flaman","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"15905","DOI":"10.1074\/jbc.271.27.15905","article-title":"An isoleucine to valine substitution in Escherichia coli acyl carrier protein results in a functional protein of decreased molecular radius at elevated pH","volume":"271","author":"Keating","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_119","first-page":"208","article-title":"Identification of a key residue in the conformational stability of acyl carrier protein","volume":"1601","author":"Keating","year":"2002","journal-title":"Biochem. Biophys. Acta"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20091328","article-title":"\u201cUnknown\u201d proteins and \u201corphan\u201d enzymes: The missing half of the engineering parts list\u2014and how to find it","volume":"425","author":"Hanson","year":"2010","journal-title":"Biochem. J"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.1093\/nar\/gkh885","article-title":"\u201cConserved hypothetical\u201d proteins: Prioritization of targets for experimental study","volume":"32","author":"Galperin","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.tibtech.2010.05.006","article-title":"From complete genome sequence to \u201ccomplete\u201d understanding?","volume":"28","author":"Galperin","year":"2010","journal-title":"Trends Biotechnol"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1021\/cr068303k","article-title":"Protein annotation at genomic scale: The current status","volume":"107","author":"Frishman","year":"2007","journal-title":"Chem. Rev"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/6\/7109\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:50:42Z","timestamp":1760219442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/6\/7109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,8]]},"references-count":123,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2012,6]]}},"alternative-id":["ijms13067109"],"URL":"https:\/\/doi.org\/10.3390\/ijms13067109","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,8]]}}}