THE BIOPHYSICAL CHARACTERISTICS AND STRUCTURAL EXPLORATION OF PROGRAMMED CELL DEATH REGULATOR B-CELL LYMPHOMA 2-ASSOCIATED X PROTEIN OF CHINESE LIVER FLUKE (CLONORCHIS SINENSIS)
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i7.19063Keywords:
B-cell lymphoma 2-associated X protein, Chinese liver fluke, Molecular model, Clonorchis sinensis, Protein structureAbstract
 Objective: The balance between deaths and cellular life is regulated by B-cell lymphoma 2 (BCL-2)-associated X protein (BAX) an important pro-apoptotic components of BCL-2 family. With this initial point, the aim of this study was to determine a comparative composite based structure of BAX of Chinese liver fluke and different structural analysis.
Methods: Protein amino acid of BAX of Chinese liver fluke mined from National Centre for Biotechnology Information (http://ncbi.nlm.nih.gov). Molecular model of BAX of Chinese liver fluke protein was generated by the comparative composite modeling tool Iterative Threading ASSEmbly Refinement suite. Afterward, I-TASSER generated molecular model was subjected to further structural improvements by energy minimization step. Distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, and hydrophobicity molecular surface analysis was performed with the help of bioinformatical tools.
Results: Analysis of Ramachandran plot created by PROCHECK tool is a consensus standard for validation purpose of protein structural modeling. Altogether 97.8% of the residues were detected in allowed and favored regions, which in turn validate the quality of generated protein structural model. Total negatively and positively charged residues within the BAX of Chinese liver fluke were 23 and 20, respectively. Chimera package-guided hydrophobicity molecular surface analysis illustrates that molecule specific hydrophobicity surface is exclusive to BAX protein molecule.
Conclusion: Within the scope of this scientific investigation, we have successfully utilized molecular modeling approach to suggest the first molecular three-dimensional model structure of BAX of Chinese liver fluke. The synchronous balance between cellular deaths and cellular life is keeping up by BAX, an important pro-apoptotic family member of BCL-2 family. Consequently, it would be an exciting approach to resolve its structural characterization and molecular structure to propose mode of mechanism action. Â
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Panda S, Chandra G. Physicochemical characterization and functional analysis of some snake venom toxin proteins and related non-toxin proteins of other chordates. Bioinformation 2012;8(18):891-6.
Miladiyah I, Jumina J, Haryana SM, Mustofa M. In silico molecular docking of xanthone derivatives as cyclooxygenase-2 inhibitor agents. Int J Pharm Pharm Sci 2017;9(3):98-104.
Murthy VB, Chowdary M, Sucharitha. In silico prediction of deleterious and non-deleterious nsSNPs in CFTR gene variants. Int J Pharm Pharm Sci 2016;8(12):303-6.
Laskowski RA, Macarthur MW, Moss DS, Thornton JM. PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Crystallogr 1993;26(2):283-91.
Wiederstein M, Sippl MJ. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 2007;35:W407-10.
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem 2004;25(13):1605-12.
Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, et al. Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science 2001;292(5517):727 30.
Xin M, Deng X. Nicotine inactivation of the proapoptotic function of BAX through phosphorylation. J Biol Chem 2005;280(11):10781-9.
Goping IS, Gross A, Lavoie JN, Nguyen M, Jemmerson R, Roth K, et al. Regulated targeting of BAX to mitochondria. J Cell Biol 1998;143(1):207-15.
Smaili SS, Hsu YT, Carvalho AC, Rosenstock TR, Sharpe JC, Youle RJ. Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling. Braz J Med Biol Res 2003;36(2):183-90.
Kim BJ, Ryu SW, Song BJ. JNK-and p38 kinase-mediated phosphorylation of BAX leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J Biol Chem 2006;281(30):21256-65.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007;57(1):43-66.
Groeger AM, Esposito V, Cassandro R, Baldi G, Rossiello L, De Luca L, et al. A model of BAX gene delivery to human lung cancer. Anticancer Res 2001;21(5):3627-30.
Xin M, Li R, Xie M, Park D, Owonikoko TK, Sica GL, et al. Small-molecule BAX agonists for cancer therapy. Nat Commun 2014;5:4935.
Petros AM, Olejniczak ET, Fesik SW. Structural biology of the Bcl-2 family of proteins. Biochim Biophys Acta 2004;1644(2-3):83-94.
Lalier L, Cartron PF, Juin P, Nedelkina S, Manon S, Bechinger B, et al. BAX activation and mitochondrial insertion during apoptosis. Apoptosis 2007;12(5):887-96.
Annis MG, Soucie EL, Dlugosz PJ, Cruz-Aguado JA, Penn LZ, Leber B, et al. BAX forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis. EMBO J 2005;24(12):2096 103.
Cartron PF, Priault M, Oliver L, Meflah K, Manon S, Vallette FM. The N-terminal end of BAX contains a mitochondrial-targeting signal. J Biol Chem 2003;278(13):11633-41.
Panda S, Kumari L. Discovery of an unexplored protein structural scaffold of serine protease from big blue octopus (Octopus cyanea): A new prospective lead molecule. Curr Drug Discov Technol 2017;17(2):1-4.
Panda S, Panda S, Kumari L. Molecular modeling and structural analysis of arylesterase of Ancylostoma duodenale. Int J Pharm Bio Sci 2016;7(3):B611-6.
Panda S, Chandra G. Sequence analysis and phylogenetic study of some toxin proteins of snakes and related non-toxin proteins of chordates. Bioinformation 2013;9(5):259-66.
Chandra G, Panda S. Molecular modeling and structural analysis of some snake venom specific toxin proteins and cognate non-toxin proteins of other chordates. Curr Drug Discov Technol 2017;14(1):59 69.
Panda S, Prasad D. Apoptosis regulator BAX of Chinese tree shrew (Tupaia belangeri Chinensis): Molecular modelling and structural characterization. Int J Pharm Bio Sci 2016;7(4):B747-52.
Panda S, Hazra S. Sequence analysis of serum paraoxonase 1 of bathyergidae family specific rats. Int J Pharm Bio Sci 2016;7(4):B702 6.
Panda S, Kumari L, Panda S. Structural understanding of cytotoxin 1 of Naja sputatrix: A potential anticancer agent. J Drug Deliv Ther 2016;6(3):59-63.
Panda S, Chandra G. Physicochemical characterization and functional analysis of some snake venom toxin proteins and related non-toxin proteins of other chordates. Bioinformation 2012;8(18):891-6.
Miladiyah I, Jumina J, Haryana SM, Mustofa M. In silico molecular docking of xanthone derivatives as cyclooxygenase-2 inhibitor agents. Int J Pharm Pharm Sci 2017;9(3):98-104.
Murthy VB, Chowdary M, Sucharitha. In silico prediction of deleterious and non-deleterious nsSNPs in CFTR gene variants. Int J Pharm Pharm Sci 2016;8(12):303-6.
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