In Silico Structural and Functional Annotation of Helicobacter Pylori (Strain Hpag1) Hypothetical Protein Hpag1_0137

Abstract

Background and Aims: Helicobacter pylori (H. pylori) is a Gram-negative pathogenic bacterium that causes gastritis in humans. The exact molecular mechanism of most of the non-annotated hypothetical proteins involved in the virulence of H. pylori is yet to be identified. This paper aims to characterize the structure and function of the non-annotated hypothetical protein (HP) HPAG1_0137 from the H. pylori bacterium (strain HPAG1) in silico. Methods: We predicted several properties of HPAG1_0137, such as its physicochemical characteristics, secondary and tertiary structures, and functional annotation using different computational tools, followed by structural validation and quality assessment. We also performed virulence, protein crystallization, and active site predictions. Results: The study found that HPAG1_0137 has 242 amino acids and an acidic pI and is thermally stable, water-soluble, and distributed in the cytoplasm. Structurally, alpha-helices and random coils are this protein’s most prominent structural components. We found structural models to be highly native and of decent quality. Conclusions: This study will facilitate a better understanding of the HPAG1_0137 protein molecular mechanism of action. In addition, it will provide the basis for additional proteomic, genomic data, and structural and pharmacological research for functional and therapeutic potential identification.

References

1. 1.Acharya D, Dutta TK. Elucidating the network features and evolutionary attributes of intraand interspecific proer JM, editor. The Proteomics Protocols Handbook. Totowa, NJ: Humana Press; 2005. p. 571-607. tein-protein interactions between hu- 10. Geourjon C, Deléage G. SOPMA: signifman and pathogenic bacteria. Sci Rep. icant improvements in protein second- 2021;11(1):190. ary structure prediction by consensus
2. 2.Kootery KP, Sarojini S. Structural and functional characterization of a hyprediction from multiple alignments. Comput Appl Biosci. 1995;11(6):681-4. pothetical protein in the RD7 region 11. Kouza M, Faraggi E, Kolinski A, in clinical isolates of Mycobacterium Kloczkowski A. The GOR Method of tuberculosis - an in silico approach to Protein Secondary Structure Prediction candidate vaccines. J Genet Eng Bioand Its Application as a Protein Aggretechnol. 2022;20(1):55. gation Prediction Tool. Methods Mol
3. 3.Galperin MY, Koonin EV. From com- Biol. 2017;1484:7-24. plete genome sequence to ‘complete’ 12. Slabinski L, Jaroszewski L, Rychlewski understanding? Trends Biotechnol. 2010;28(8):398-406.
4. 4.Ashrafi H, Siraji MI, Showva NN, Hossain MM, Hossan T, Hasan MA, et al. L, Wilson IA, Lesley SA, Godzik A. XtalPred: a web server for prediction of protein crystallizability. Bioinformatics. 2007;23(24):3403-5. Structure to function analysis with an- 13. Waterhouse A, Bertoni M, Bienert tigenic characterization of a hypotheti- S, Studer G, Tauriello G, Gumiencal protein,HPAG1_0576 from Helicony R, et al. SWISS-MODEL: homolbacter pylori HPAG1. Bioinformation. ogy modelling of protein structures 2019;15(7):456-66. and complexes. Nucleic Acids Res.
5. 5.Segelke BW. Functional Annotation 2018;46(W1):W296-W303. from Structural Homology. Methods 14. Kelley LA, Mezulis S, Yates CM, Mol Biol. 2022;2349:215-57.
6. 6.Gasteiger E, Hoogland C, Gattiker A, Duvaud Se, Wilkins MR, Appel RD, et al. Protein Identification and Analysis 10 Wass MN, Sternberg MJ. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015;10(6):845-58. In silico structural and functional annotation of Helicobacter pylori (strain HPAG1) hypothetical protein HPAG1_0137 Majmaah Journal of Health Sciences ,Vol. 11, Issue 2, April - 2023, Ramadan - 1444
7. 7.Colovos C, Yeates TO. Verification 2004;13(5):1402-6. of protein structures: patterns of non- 22. Yu NY, Wagner JR, Laird MR, Melli G, bonded atomic interactions. Protein Rey S, Lo R, et al. PSORTb 3.0: imSci.1993;2(9):1511-9. proved protein subcellular localization
8. 8.Eisenberg D, Lüthy R, Bowie JU. VER- prediction with refined localization IFY3D: assessment of protein models subcategories and predictive capabiliwith three-dimensional profiles. Methties for all prokaryotes. Bioinformatics. ods Enzymol. 1997;277:396-404. 2010;26(13):1608-15.
9. 9.Anderson RJ, Weng Z, Campbell RK, 23. Gupta A, Kapil R, Dhakan DB, SharJiang X. Main-chain conformational ma VK. MP3: a software tool for the tendencies of amino acids. Proteins. prediction of pathogenic proteins in 2005;60(4):679-89. genomic and metagenomic data. PLoS
10. 10.Wiederstein M, Sippl MJ. ProSA-web: One. 2014;9(4):e93907. interactive web service for the rec- 24. Mistry J, Chuguransky S, Williams L, ognition of errors in three-dimen- Qureshi M, Salazar GA, Sonnhammer sional structures of proteins. Nucle- ELL, et al. Pfam: The protein families ic Acids Res. 2007;35(Web Server database in 2021. Nucleic Acids Res. issue):W407-10. 2021;49(D1):D412-D9.
11. 11.Jendele L, Krivak R, Skoda P, Novotny 25. Blum M, Chang HY, Chuguransky S, M, Hoksza D. PrankWeb: a web serv- Grego T, Kandasaamy S, Mitchell A, er for ligand binding site prediction et al. The InterPro protein families and and visualization. Nucleic Acids Res. domains database: 20 years on. Nucleic 2019;47(W1):W345-W9. Acids Res. 2021;49(D1):D344-D54.
12. 12.Yu CS, Chen YC, Lu CH, Hwang JK. 26. Lu S, Wang J, Chitsaz F, Derbyshire Prediction of protein subcellular locali- MK, Geer RC, Gonzales NR, et al. zation. Proteins. 2006;64(3):643-51. CDD/SPARCLE: the conserved do-
13. 13.Yu CS, Lin CJ, Hwang JK. Predictmain database in 2020. Nucleic Acids ing subcellular localization of pro- Res. 2020;48(D1):D265-D8. teins for Gram-negative bacteria by 27. Rabbi MF, Akter SA, Hasan MJ, Amin support vector machines based on A. In Silico Characterization of a Hypon-peptide compositions. Protein Sci. thetical Protein from. Bioinform Biol In- In Silico Structural and Functional Annotation of Helicobacter Pylori (Strain Hpag1) Hypothetical Protein Hpag1_0137 11 Majmaah Journal of Health Sciences ,Vol. 11, Issue 2, April - 2023, Ramadan - 1444 sights. 2021;15:11779322211011140. protein TRIF/TICAM-1. Acta Crystal-
14. 14.Alaidarous M. In silico structural holographica Section F-Structural Biolmology modeling and characterization of multiple N-terminal domains ogy and Crystallization Communications.2013;69:766-70. of selected bacterial Tcps. PeerJ. 35. Li FM, Gao XW. Predicting Gram-Pos2020;8:e10143.
15. 15.Bhagavan NV, Ha C-E. Essentials of medical biochemistry: with clinical casitive Bacterial Protein Subcellular Location by Using Combined Features. Biomed Res Int. 2020;2020:9701734. es. 1st ed. Amsterdam ; Boston: Elsevi- 36. Py B, Barras F. Building Fe-S proteins: er/Academic Press; 2011. xvii, 581 p. p.
16. 16.Bojkowska K, Santoni de Sio F, Barde bacterial strategies. Nat Rev Microbiol. 2010;8(6):436-46. I, Offner S, Verp S, Heinis C, et al. Measuring in vivo protein half-life. Chem Biol. 2011;18(6):805-15.
17. 17.Moran MA, Satinsky B, Gifford SM, Luo H, Rivers A, Chan LK, et al. Sizing up metatranscriptomics. ISME J. 2013;7(2):237-43.
18. 18.Holcomb J, Spellmon N, Zhang Y, Doughan M, Li C, Yang Z. Protein crystallization: Eluding the bottleneck of X-ray crystallography. AIMS Biophys.2017;4(4):557-75.
19. 19.Jia Q, Zeng H, Zhang J, Gao S, Xiao N, Tang J, et al. The Crystal Structure of the. Insects. 2021;12(7).
20. 20.Ullah MO, Ve T, Dkhar J, Alaidarous M, Ericsson DJ, Sweet MJ, et al. Crystallization and X-ray diffraction analysis of the N-terminal domain of the Toll-like receptor signalling adaptor 12 In silico structural and functional annotation of Helicobacter pylori (strain HPAG1) hypothetical protein HPAG1_0137