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Structural and Functional Analysis of Ferritin Heavy Chain Subunit In www.symbiosisonlinepublishing.com Symbiosis ISSN Online: 2374-8362 Research Article Journal of Advanced Research in Biotechnology Open Access Structural and Functional Analysis of Ferritin Heavy Chain Subunit in Oryzias latipes Ajit Tiwari1*, A D Upadhyay1, Himanshu Priyadarshi2, A K Roy1, Rumpi Ghosh1, Suresh Yambem2 and Dibyajyoti Uttameswar Behera2 1Bioinformatics Centre, College of Fisheries, CAU (I), Lembucherra, Tripura 2Dept of Fish Genetics and Reproduction (FGR), College of Fisheries, CAU (I), Lembucherra, Tripura Received: June 25, 2019; Accepted: July 12, 2019; Published: July 22, 2019 *Corresponding author: Ajit Tiwari, Bioinformatics Centre, College of Fisheries, CAU (I), Lembucherra, Tripura. protein from bacteria to human which emphasize their biological Abstract In North East region of India, iron toxicity is one of the major Inimportance eukaryotes, [6]. it Itconsists forms aof hollow24 protein shell subunits with a cavitywith molecular of 80 A1 diameters that can store up to 4,500 Fe (III) atoms as a biomineral. problems in culture fisheries. To overcome this challenge, it is Fenecessary binding to site identify in the the fourth role ofhelix ferritin that proteininteracts as with an iron oxygen. detoxificant In this weight of 450 kDa [7, 8, 9]. In mammals, ferritin molecules of and store in fishes. The Heavy chain in a ferritin protein possess di- paper attempt has been made to study the structure and function heavy (H) and light (L) chain subunits having molecular masses of ferritin heavy chain subunit of from amino acid Oryzias latipes of 21 and 19 kDa. Heavy chains are important for Fe (II) oxidation, sequence. Physicochemical characterization by Expasy ProtParam form tools reveals that the protein is acidic, unstable and hydrophilic. assemblewhereas Lightin different chains ratios assist to in form iron a proteinnucleation, shell mineralization, of 24 subunits capableand long-term of acquiring storage iron [9]. Theatoms. Heavy Key and features Light chainthat differentiatesubunits co- di-Fe binding site in H chain that interacts the fourth helix oxygen A hydropathy scale showed two peak with significant score above the threshold value (0 to + value) but TMHMM conclude that there were one transmembrane domain within protein. The secondary structures For example, H-chains are abundant in heart tissues that involved contain alpha helix (56.50%), extended strands (10.73%) and coiled and is responsible for the ferroxidase activity of the protein [10]. region (32.77%). The query sequence shows homology to the selected bass, with functional involvement in both iron metabolism and template (structure of mouse heavy chain modified ferritin by Oryzias X-ray in a rapid exchange of iron [11]. The dual role of ferritin in sea latipesdiffraction and technique)Oryzias melastigma with maximum for the ferritin% identity. heavy To sub analyse unit along the phylogenetic relationship, ML tree was constructed between immuneFerritin response, heavy waschain also subunit reported with by the the variableresearcher sequence [12]. is observed between same genus species and the out crossed species. generally used for determining phylogenetic relationships among with Cyprinus carpio as out crossed. Two distinct clads formation was different organisms. It is considered to be useful in determining relationships within families and genera. A Comparative analysis domain,In protein-protein one Uniprot interaction keywords analysis and eleven via STRINGfunctional 10.0 parameters tool, two enriched pathways of KEGG, six Inter Pro Oryziasdomains, latipes one PFAM protein investigation reveals the structural features and their association in generates evolutionary relationship and new classification of network analysis were identified in . The overall schemes. The vertebrates mitochondrial DNA are more detoxificationKeywords: and Ferritin iron homeostasis. Heavy Chain; Oryzias latipes; Physicochemical polymorphic and more useful for the identification of species and can evolve faster in comparison to nuclear Oryzias DNA latipes [13]. , is a small, bony, laying an egg in fresh water, native to Asian countries. It Characterization; Homology Modeling occurs,The coastalMedaka waters fish, scientific having highname adaptability and it collected Introduction in wide range especially from brackish, mangrove swamps, Iron, required as a trace element in living organisms, forms metallo protein in conjugation with different proteins. However, excess iron in an aquatic ecosystem become toxic and acts as a usedacidic infreshwater, the area forestof genomics, streams, genetics, canals, ricedisease field, model, basins sex of catalyst in the Fenton reaction generating free radicals which determination,rivers, pools, and reproduction oxbows [14]. and The evolution. Medaka Inis apresent model study,organism the structural model, protein-protein interaction and physicochemical stores in a nontoxic and reversible form and central to iron properties of ferritin H chain protein sequence (accession number are harmful to fishes. [1] Ferritin is the ubiquitous protein which Oryzias latipes were analyzed to determine the structural and functional role in Fishes. metabolism [2]. Thus, it has an important role in iron storage and XP_020569048.2.) of detoxification [3, 4, 5]. Ferritin is structurally highly conserved Symbiosis Group *Corresponding author email: Copyright: Structural and functional analysis of ferritin heavy chain subunit in Oryzias latipes © 2019 Ajit Tiwari,et al. Material and Methods (NJ) with complete gap deletion, Poisson substitution model, Sequence retrieval rateswas established among sites among (uniform different rates), fish the species pattern by Neighbor-joining among lineages Oryzias latipes was retrieved from National Center for The amino acid sequence of Ferritin heavy subunit of model (Homogeneous)Protein-protein and interactions 1000 bootstrap replications. fish Biotechnology Information (NCBI) database having the accession number XP_020569048.2. It was verified by peptide search in the The Search Tool for the Retrieval of Interacting Genes/ Proteins UniProtPhysicochemical KB and found properties entry no. H2LMW5. and Secondary structure from(STRING different 10.0) database sources, (http://string-db.org/) including experimental was used repositories, to predict prediction computationalthe interacting predictionproteins [29]. methods, The database and public contains text groups. information Results The physicochemical properties including molecular weight, Physicochemical properties theoretical pI, the % of the amino acid composition, total number estimated half-life, atomic composition, aliphatic index, instability A physicochemical property of Ferritin heavy chain subunit of indexof residue grand in average negative of andhydropath positive city form, of the extinction ferritin heavy coefficient, chain Oryzias latipes was analyzed by the Expasy ProtParam server. It protein of Oryzias latipes ProtParam server. [15] was estimated using Expasy was 177 amino acid long proteins with the estimated molecular weight 20880.39 kDa respectively. The isoelectric point (pI) The secondary structures of the ferritin heavy chain subunit of ferritin protein was 5.54 which revealed that ferritin heavy werePrediction predicted via by ProtScale PSIPRED [16] and GORIV methodology [17]. chain was acidic. The amino acid composition showed the chargedmaximum and presence positively of Leucine charged (11.3%) residues and of minimumFerritin are presence (Asp+ of Tryptophan (1.1%) (Table 1). The total number of negatively The protein sequence was input in the FASTA format and the Table 1: Amino acid composition of Ferritin heavy chain subunit of amino acid scale selected was Hphob /Kyte & Doolittle [18] with Oryzias latipes the window size of 19 as detection of hydrophobic, membrane- tool is available at the bioinformatics resource portal ExPASy Amino acids No. s Percentage (Expertspanning Protein domains Analysis is best System). suited at this 30 window. The ProtScale Ala (A) Prediction via TMHMM 10 5.6% AsnArg (N)(R 10 5.6% transmembraneTMHMM is an helices online andtool canused discriminate to predict membrane between proteinsoluble 11 6.2% andtopology membrane based proteinson a hidden with Markovhigh degree model of [19].accuracy. It predicts It can AspCys (C)(D) 13 7.3% 5 2.8% correctly predict 97-98 % of the transmembrane helices. The Gln (Q) 12 6.8% FASTA sequence of the query protein was used as input with all Glu (E) 17 9.6% the parameters set to default. TMHMM Server version 2.0 was HisGly (H)(G) 9 5.1% usedTertiary (Figure structure 5.0). prediction Ile (I) 106 5.6% 20 3.4% Tertiary structure of ferritin was analyzed with a template Leu (L) 11.3% search for the query protein through PDB sum database [20]. This Lys (K) 116 6.2% result was cross verified by SWISSMODEL/Workspace, which displayed sequence identity with the query sequence [21]. By MetPhe (M)(F) 8 3.4% homology modeling, 3-D structure of ferritin heavy subunit was Pro (P) 3 4.5% predicted through Swiss model [22, 23], Phyre 2 [24] and pymol Ser (S) 1.7% software [25] and Raptor X [26]. The predicted structure of the 3 ferritin heavy subunit was validated through Ramachandran plot 9 5.1% byPhylogenetic utilizing rampage analysis server [27]. Thr (T) 2 1.7% Phylogenetic analysis of fth based on amino acid sequences Trp (W) 7 1.1% Tyr (Y) 4.0% was carried out using the software Molecular Evolutionary PylVal (O)(V) 50 2.8% Genetic Analysis (MEGA; version 7) [28]. Sequences were
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