Identification of disordered regions and potential active sites from3-hydroxy-3-methylglutaryl-CoA reductase of Triticum aestivum L. using theoretical approach

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Identification of disordered regions and potential active sites from3-hydroxy-3-methylglutaryl-CoA reductase of Triticum aestivum L. using theoretical approach

Utpal Kumar Adhikari, Ferozur Rahman, Mostaq Ahmmed, Razib Chowdhury, M. Mizanur Rahman
Int. J. Biosci.10( 1), 24-41, January 2017.
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Abstract

3-hydroxy-3-methylglutaryl CoA reductase is considered as an essential enzyme due to its inevitability in the Mevalonate pathway for the synthesis of isoprenoids in plants. In this study, theoretical investigations were accomplished for comparative protein model and active site analyses of Triticum aestivum HMG-CoA reductase (designated as TaHMGR) as there are no three-dimensional structures available for this species in Protein Data Bank. So, to fulfill the necessity of this structure we built the comparative protein model, evaluated using different criteria and finally deposited in Protein Model Database (PMDB). We used different Bioinformatics tools and servers to carry out this research. The selected enzyme contains disordered regions and the residues Glycine, Serine, Lysine, and Proline are mainly responsible for these regions as found by our research. We also found 3 ligand binding sites with the high quantity of Glycine, Valine, and Alanine residues in their binding sites and the significant Z-score ensures these findings. The biochemical function was found as a catalytic and binding activity with the significance score, which confirms the actual function of TaHMGR. The attained data convey necessary fundamental information about this enzyme to pave the way in improving the structure-based drug development using T. aestivum species.

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Adhikari UK, Hossain S, Rahman MM. 2015. Investigations on 3-hydroxy-3-methylglutaryl CoA reductase enzyme from different source organisms. Journal of Nature Science and  Sustainable Technology 9, 725–735.

Altschul SF, Wootton JC, Gertz EM. 2005. Protein Database Searches Using Compositionally Adjusted Substitution Matrices. FEBS Journal 272, 5101–5109. http://dx.doi.org/10.1111/j.1742-4658.2005.04945.x

Andrade-Pavón D, Sánchez-Sandoval E, Rosales-Acosta B, Ibarra JA, Tamariz J, Hernández-Rodríguez C, Villa-Tanaca L. 2014.  The 3-hydroxy-3-methylglutaryl coenzyme-A reductases from fungi: a proposal as a therapeutic target and as a study model. Revista Iberoamericana de Micología 31, 81–5. http://dx.doi.org/10.1016/j.riam.2013.10.004

Aoyagi K, Beyou A, Moon K, Fang L, Ulrich T. 1993. lsolation and Characterization of cDNAs Encoding Wheat 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase. Plant physiology 102, 623–628.

Benkert P, Biasini M, Schwede T. 2011. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27, 343–350. http://dx.doi.org/10.1093/bioinformatics/btq662

Berjanskii M, Zhou J, Liang Y, Lin G, Wishart DS. 2012. Resolution-by-proxy: a simple measure for assessing and comparing the overall quality of NMR protein structures. Journal of biomolecular NMR 53, 167–180. http://dx.doi.org/10.1007/s10858-012-9637-2

Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Schwede T. 2014. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Research 42, W252–8. http://dx.doi.org/10.1093/nar/gku340

Bjellqvist B, Hughes GJ, Pasquali C, Paquet N, Ravier F, Sanchez JC, Hochstrasser D. 1993. The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences. Electrophoresis 14, 1023–1031.

Blom N, Gammeltoft S, Brunak S. 1999. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. Journal of molecular biology 294, 1351–1362. http://dx.doi.org/10.1006/jmbi.1999.3310

Campos N, Arro M, Ferrer A, Boronat A. 2014. Determination of 3-hydroxy-3-methylglutaryl CoA reductase activity in plants. Plant Isoprenoids: Methods and Protocols 1153, 21–40. http://dx.doi.org/10.1007/978-1-4939-0606-2_3

Castrignano T. 2006. The PMDB Protein Model Database. Nucleic Acids Research 34, D306–D309. http://dx.doi.org/10.1093/nar/gkj105

Chen X, Wang X, Li Z, Kong L, Liu G, Fu J, Wang A. 2012. Molecular cloning, tissue expression and protein structure prediction of the porcine 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) gene. Gene 495, 170–7. http://dx.doi.org/10.1016/j.gene.2011.12.051

Cojocaru E, Zamfir CL, Lupuşoru CE, Cotuţiu C. 2010. The effects of some nonpolar aminoacids–valine, leucine–administration on the arterial wall already exposed to a hypercholesterolemic diet. Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi, 114, 504—509.

Colovos C, Yeates TO. 1993. Verification of protein structures: patterns of nonbonded atomic interactions. Protein Science 2, 1511–1519. http://dx.doi.org/10.1002/pro.5560020916

Dale S, Arró M, Becerra B, Morrice NG, Boronat A, Hardie DG, Ferrer A. 1995.  Bacterial expression of the catalytic domain of 3-hydroxy-3-methylglutaryl-CoA reductase (isoform HMGR1) from Arabidopsis thaliana, and its inactivation by phosphorylation at Ser577 by Brassica oleracea 3-hydroxy-3-methylglutaryl-CoA reductase kinase. European Journal of Biochemistry 233, 506–513. http://dx.doi.org/10.1111/j.1432-1033.1995.506_2.x

Darabi M, Izadi-Darbandi A, Masoudi-Nejad A. 2012. Bioinformatics study of the 3-hydroxy-3-methylglotaryl-coenzyme A reductase (HMGR) gene in Gramineae. Molecular biology reports 39, 8925—8935. http://dx.doi.org/10.1007/s11033-012-1761-2

Darabi M, Seddigh S. 2013. Conserved motifs identification of 3-hydroxy-3-methylglotaryl-coenzyme A reductase (HMGR ) protein in some different species of drosophilidae by bioinformatics tools. Annals of Biological Research 4, 158–163.

Dunker AK, Obradovic Z. 2001. The protein trinity–linking function and disorder. Nature Biotechnology 19, 805—806. http://dx.doi.org/10.1038/nbt0901-805.

Dyson HJ, Wright PE. 2005. Intrinsically unstructured proteins and their functions. Nature Reviews Molecular Cell Biology 6, 197—208. http://dx.doi.org/10.1038/nrm1589.

Edgar RC, Drive RM, Valley M. 2004. MUSCLE : multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Research 32, 1792–1797. http://dx.doi.org/10.1093/nar/gkh340

Eswar N, Webb B, Marti-Renom MA. 2006. Comparative Protein Structure Modeling Using Modeller. Current protocols in bioinformatics  5, 5–6. http://dx.doi.org/10.1002/0471250953.bi0506s15

Felsenstein J. 1985. Confidence Limits on Phylogenies: An Approach Using the Bootstrap. Evolution (N Y) 39, 783–791.

Friesen JA, Rodwell VW. 2004. The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases. Genome Biology 5, 248. http://dx.doi.org/10.1186/gb-2004-5-11-248

Gasteiger E, Hoogland C, Gattiker A, Duvaud SE, Wilkins MR, Appel RD, Bairoch A. 2005.  Protein Identification and Analysis Tools on the ExPASy Server. Proteomics Protoc Handb, Humana Press, 571-607. http://dx.doi.org/10.1385/1-59259-890-0:571

Gelly J-C, Joseph AP, Srinivasan N, de Brevern AG. 2011. iPBA: a tool for protein structure comparison using sequence alignment strategies. Nucleic Acids Research 39, W18–W23. http://dx.doi.org/10.1093/nar/gkr333

Gill SC, von Hippel PH. 1989. Calculation of protein extinction coefficients from amino acid sequence data. Analytical biochemistry 182, 319–326.

Guex N, Peitsch MC. 1997. SWISS-MODEL and the Swiss-Pdb Viewer: An environment for comparative protein modeling. Electrophoresis 18, 2714–2723. http://dx.doi.org/10.1002/elps.1150181505

Guruprasad K, Reddy B V, Pandit MW. 1990. Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence. Protein engineering 4, 155–161. http://dx.doi.org/10.1093/protein/4.2.155

Ha SH, Kim JB, Hwang YS, Lee SW. 2003. Molecular characterization of three 3-hydroxy-3-methylglutaryl-CoA reductase genes including pathogen-induced Hmg2 from pepper (Capsicum annuum). Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression 1625, 253—260. http://dx.doi.org/10.1016/s0167-4781(02)00624-3

Huang B. 2009. MetaPocket: a meta approach to improve protein ligand binding site prediction. OMICS 13, 325—330. http://dx.doi.org/10.1089/omi.2009.0045\

Ikai A. 1980. Thermostability and aliphatic index of globular proteins. Journal of biochemistry 88, 1895–1898.

Ingale AG, Goto S. 2014. Prediction of CTL epitope, in silico modeling and functional analysis of cytolethal distending toxin (CDT) protein of Campylobacter jejuni. BMC Research Notes 7, 92. http://dx.doi.org/10.1186/1756-0500-7-92

Ishida T, Kinoshita K. 2008. Prediction of disordered regions in proteins based on the meta approach. Bioinformatics 24, 1344—1348. http://dx.doi.org/10.1093/bioinformatics/btn195

Istvan E. 2000. The structure of the catalytic portion of human HMG-CoA reductase. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1529, 9–18. http://dx.doi.org/10.1016/S1388-1981(00)00134-7

Istvan ES, Deisenhofer J. 2001. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292, 1160–1164. http://dx.doi.org/10.1126/science.1059344

Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J. 2000. Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO Journal 19, 819–830. http://dx.doi.org/10.1093/emboj/19.5.819

Jiang J, Kai G, Cao  X, Chen F, He D, Liu Q. 2006.Molecular cloning of a HMG-CoA reductase gene from Eucommia ulmoides Oliver. Bioscience Reports 26, 171–81. http://dx.doi.org/10.1007/s10540-006-9010-3

Joseph AP, Agarwal G, Mahajan S, Gelly JC, Swapna LS, Offmann B, Schneider B. 2010.  A short survey on protein blocks. Biophysical Reviews 2, 137—147. http://dx.doi.org/10.1007/s12551-010-0036-1

Kalita R, Patar L, Shasany AK, Modi MK, Sen P. 2015. Molecular cloning, characterization and expression analysis of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Centella asiatica L. Molecular biology reports 42, 1431-1439.

Kiran U, Ram M, Mather Ali Khan SK, Jha P, Alam A, Abdin MZ. 2010.Structural and functional characterization of HMG-COA reductase from Artemisia annua. Bioinformation 5, 146–149. http://dx.doi.org/10.6026/97320630005146

Korth KL, Jaggard DAW, Dixon RA. 2000. Developmental and light-regulated post-translational control of 3-hydroxy-3-methylglutaryl-CoA reductase levels in potato. The Plant Journal 23, 507–516. http://dx.doi.org/10.1046/j.1365-313x.2000.00821.x

Kyte J, Doolittle RF. 1982. A simple method for displaying the hydropathic character of a protein. Journal of molecular biology 157, 105–132. http://dx.doi.org/10.1016/0022-2836(82)90515-0

Labarga A, Valentin F, Anderson M, Lopez R. 2007. Web services at the European bioinformatics institute. Nucleic Acids Research 35, W6—11. http://dx.doi.org/10.1093/nar/gkm291

Laskowski RA. 2004. PDBsum more: new summaries and analyses of the known 3D structures of proteins and nucleic acids. Nucleic Acids Research 33, D266–D268. http://dx.doi.org/10.1093/nar/gki001

Leivar P, González VM, Castel S, Trelease RN, López-Iglesias C, Arró M, Fernandez-Busquets X. 2005. Subcellular Localization of Arabidopsis 3-Hydroxy-3-Methylgluraryl-Coenzyme A Reductase. Plant physiology 137, 57–69. http://dx.doi.org/10.1104/pp.104.050245.far

Li W, Liu W, Wei H, He Q, Chen J, Zhang B, Zhu S. 2014.Species-specific expansion and molecular evolution of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) gene family in plants. PLoS One 9, e94172. http://dx.doi.org/10.1371/journal.pone.0094172

Liao Z, Tan Q, Chai Y, Zuo K, Chen M, Gong Y, Tang K. 2004. Cloning and characterisation of the gene encoding HMG-CoA reductase from Taxus media and its functional identification in yeast. Functional Plant Biology 31, 73. http://dx.doi.org/10.1071/FP03153

Linding R, Russell RB, Neduva V, Gibson TJ. 2003. GlobPlot: Exploring protein sequences for globularity and disorder. Nucleic Acids Research 31, 3701–3708. http://dx.doi.org/10.1093/nar/gkg519

Lovell SC, Davis IW, Arendall WB, de Bakker PI, Word JM, Prisant MG, Richardson DC. 2003.  Structure validation by Cα geometry: ϕ,ψ and Cβ deviation. Proteins: Structure, Function, and Bioinformatics 50, 437–450. http://dx.doi.org/10.1002/prot.10286

Luskey KL, Stevens B. 1985. Human 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase. Journal of Biological Chemistry 260, 10271–10277.

Lüthy R, Bowie JU, Eisenberg D. 1992. Assessment of protein models with three-dimensional profiles. Nature 356, 83–85. http://dx.doi.org/10.1038/356083a0

McGuffin LJ, Bryson K, Jones DT. 2000. The PSIPRED protein structure prediction server. Bioinformatics 16,404–405. http://dx.doi.org/10.1093/bioinformatics/16.4.404

Nishikawa S, Hirata A, Nakano A. 1994. Inhibition of endoplasmic reticulum (ER)-to-Golgi transport induces relocalization of binding protein (BiP) within the ER to form the BiP bodies. Molecular biology of the cell 5, 1129–1143.

Obradovic Z, Peng K, Vucetic S, Radivojac P, Dunker AK. 2005. Exploiting heterogeneous sequence properties improves prediction of protein disorder. Proteins: Structure, Function, and Bioinformatics 61, 176-182. http://dx.doi.org/10.1002/prot.20735

Oldfield CJ, Ulrich EL, Cheng Y, Dunker AK, Markley JL. 2005. Addressing the intrinsic disorder bottleneck in structural proteomics. Proteins: Structure, Function, and Bioinformatics 59, 444-453. http://dx.doi.org/10.1002/prot.20446

Orosz F, Ovádi J. 2011. Proteins without 3D structure: definition, detection and beyond. Bioinformatics 27, 1449—1454. http://dx.doi.org/10.1093/bioinformatics/btr175

Saitou N, Nei M. 1987. The neighbour-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evo 4, 406–425.

Sarma K, Dehury B, Sahu J, Sarmah R, Sahoo S, Sahu M, Barooah M. 2012. A comparative proteomic approach to analyse structure, function and evolution of rice chitinases: a step towards increasing plant fungal resistance. Journal of Molecular Modeling 18, 4761—4780. http://dx.doi.org/10.1007/s00894-012-1470-8

Stormo C, Kringen MK, Grimholt RM, Berg JP, Piehler AP. 2012.  A novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) splice variant with an alternative exon 1 potentially encoding an extended N-terminus. BMC molecular biology 13, 29. http://dx.doi.org/10.1186/1471-2199-13-29

Tamura K, Stecher G, Peterson D. 2013. MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0. Molecular biology and evolution 30, 2725–2729. http://dx.doi.org/10.1093/molbev/mst197

Theivagt AE, Amanti EN, Beresford NJ, Tabernero L, Friesen JA. 2006. Characterization of an HMG-CoA Reductase from Listeria monocytogenes That Exhibits Dual Coenzyme Specificity. Biochemistry 45, 14397–14406. http://dx.doi.org/10.1021/bi0614636

Thompson JD, Higgins DG, Gibson TJ. 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research 22, 4673–4680. http://dx.doi.org/10.1093/nar/22.22.4673

Trost B, Kusalik A. 2011. Computational prediction of eukaryotic phosphorylation sites. Bioinformatics 27, 2927—2935. http://dx.doi.org/10.1093/bioinformatics/btr525

Wadood A, Riaz M, Shams S. 2014. Structural Modeling and Molecular Dynamics Simulation Studies of Camel Milk Kappa Casein Protein. International Journal of Computational Bioinformatics and In Silico Modeling 3, 483–490.

Wang Y, Chen S, Li H. 2010. Hydrogen peroxide stress stimulates phosphorylation of FoxO1 in rat aortic endothelial cells. Acta pharmacologica Sinica 31, 160—164. http://dx.doi.org/10.1038/aps.2009.201

Wiederstein M, Sippl MJ. 2007. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research 35, W407–W410. http://dx.doi.org/10.1093/nar/gkm290

Zhang J, Johnson GV. 2000. Tau protein is hyperphosphorylated in a site-specific manner in apoptotic neuronal PC12 cells. Journal of neurochemistry 75, 2346—2357. http://dx.doi.org/10.1046/j.14714159.2000.0752346.x

Zhang L, Wang JT, Zhang DW, Zhang G, Guo SX. 2014. Molecular characterization of a HMG-CoA reductase gene from a rare and endangered medicinal plant, Dendrobium officinale. Yao xue xue bao= Acta pharmaceutica Sinica 49, 411—418.

Zhang Z, Li Y, Lin B, Schroeder M, Huang B. 2011. Identification of cavities on protein surface using multiple computational approaches for drug binding site prediction. Bioinformatics 27, 2083—2088. http://dx.doi.org/10.1093/bioinformatics/btr331