2016 Volume 3 Issue 4

Structure study and predict the function of the diphtheria toxin in different pH levels (Acidic-Basic-Natural) using molecular dynamics simulations

Soheila Ghaderi, Mohammad Reza Bozorgmehr, Ali Morsali

Conformational switching is broadly defined as an alteration in the spatial organization of a macromolecule in response to environmental change. This study was performed to establish the relationship between variable pH and structural and functional aspect of the diphtheria toxin (DT). Molecular dynamics (MD) simulations were performed at different pH levels (4, 6.5, and 10) consist of a DT structure in water at 300K and salt concentration 0.25M at 100ns timescale simulation. Results showed that fluctuations were changed in the key residues at different pH levels. Fluctuations were more profound in the fragments A and B of DT at pH4 compared with pH6.5 and pH10. Fluctuations in the fragment A of DT (DTA) were obtained at pH4 including residues Ser9, Pro25, Tyr46, Leu73, Arg173, and Ala187. The average of the radius of gyration (Rg) and the root mean square deviation (RMSD) of the DT structure showed that decreased at pH 6.5 in comparison with pH4 and pH10. Results showed conformational changes of DT structure at pH4 compared with pH6.5 and pH10.


Keywords: Chain B of Diphtheria Toxin; Chain A of Diphtheria Toxin; Molecular dynamics simulation; Root mean square fluctuation; Variable pH;


Mertz JE, Pettitt BM. International Journal of High Performance Computing Applications. 1994;8(1):47-53.

Bürgi R, Kollman PA, van Gunsteren WF. Proteins: Structure, Function, and Bioinformatics. 2002;47(4):469-80.

Choe S, Bennett MJ, Fujii G, Curmi PM, Kantardjieff KA, Collier RJ, et al. The crystal structure of diphtheria toxin. 1992.

Oh KJ, Zhan H, Cui C, Hideg K, Collier RJ, Hubbell WL. Science. 1996;273(5276):810-2.

Menestrina G, Schiavo G, Montecucco C. Molecular aspects of medicine. 1994;15(2):79-193.

Draper RK, Simon MI. The Journal of cell biology. 1980;87(3):849-54.

Marnell MH, Shia S, Stookey M, Draper RK. Infection and immunity. 1984;44(1):145-50.

Middlebrook JL, Dorland RB. Microbiological reviews. 1984;48(3):199.

Sandvig K, Olsnes S. The Journal of cell biology. 1980;87(3):828-32.

Blewitt MG, Chung LA, London E. Biochemistry. 1985;24(20):5458-64.

Dumont M, Richards F. Journal of Biological Chemistry. 1988;263(4):2087-97.

Hu VW, Holmes RK. Biochimica et Biophysica Acta (BBA)-Biomembranes. 1987;902(1):24-30.

Sandvig K, Olsnes S. Journal of Biological Chemistry. 1981;256(17):9068-76.

Kagan BL, Finkelstein A, Colombini M. Diphtheria toxin fragment forms large pores in phospholipid bilayer

membranes. Proceedings of the National Academy of Sciences. 1981;78(8):4950-4.

Zalman LS, Wisnieski BJ. Mechanism of insertion of diphtheria toxin: peptide entry and pore size determinations. Proceedings of the National Academy of Sciences. 1984;81(11):3341-5.

Papini E, Sandona D, Rappuoli R, Montecucco C. The EMBO journal. 1988;7(11):3353.

Sandvig K, Olsnes S. Journal of Biological Chemistry. 1988;263(25):12352-9.

Eisenberg D, Schwarz E, Komaromy M, Wall R. Journal of molecular biology. 1984;179(1):125-42.

Kurnikov IV, Kyrychenko A, Flores-Canales JC, Rodnin MV, Simakov N, Vargas-Uribe M, et al. Journal of molecular biology. 2013;425(15):2752-64.

Jiang JX, Abrams FS, London E. Biochemistry. 1991;30(16):3857-64.

Strom CS, Liu XY, Jia Z. Biophysical journal. 2005;89(4):2618-27.

James JJ, Lakshmi BS, Raviprasad V, Ananth MJ, Kangueane P, Gautam P. Protein engineering. 2003; 16(12):1017-24.

Steere B, Eisenberg D. Biochemistry. 2000;39(51):15901-9.

Guex N, Peitsch MC. electrophoresis. 1997;18(15):2714-23.

Hess B, Kutzner C, Van Der Spoel D, Lindahl E. Journal of chemical theory and computation. 2008;4(3):435-47.

Satpathy R, Guru RK, Behera R, Priyadarshini A. J Comput Sci Syst Biol. 2010;3(3).

Parrinello M, Rahman A, Vashishta P. Physical review letters. 1983;50(14):1073.

Bussi G, Donadio D, Parrinello M. The Journal of chemical physics. 2007;126(1):014101.

Darden T, York D, Pedersen L. The Journal of chemical physics. 1993;98(12):10089-92.

Hess B, Bekker H, Berendsen HJ, Fraaije JG. Journal of computational chemistry. 1997;18(12):1463-72.

Miyamoto S, Kollman PA. Journal of computational chemistry. 1992;13(8):952-62.

Falconi M, Biocca S, Novelli G, Desideri A. BMC structural biology. 2007;7(1):73.

Gilis D, Rooman M. Journal of molecular biology. 1997;272(2):276-90.

Honjo T, Nishizuka Y, Hayaishi O, Kato I. Journal of Biological Chemistry. 1968;243(12):3553-5.

Duncan AM, Heddle JA. Cancer letters. 1984;23(3):307-11.

Collier R, Kandel J. Structure and Activity of Diphtheria Toxin I. Journal of Biological Chemistry. 1971;246(5):1496-503.

Drazin R, Kandel J, Collier R. Journal of Biological Chemistry. 1971;246(5):1504-10.

Gill DM, Pappenheimer A. Journal of Biological Chemistry. 1971;246(5):1492-5.

Gill DM, Dinius LL. Journal of Biological Chemistry. 1971;246(5):1485-91.

Silverman J, Mindell J, Zhan H, Finkelstein A, Collier R. The Journal of membrane biology. 1994;137(1):17-28.

Ghatak C, Rodnin MV, Vargas-Uribe M, McCluskey AJ, Flores-Canales JC, Kurnikova M, et al. Role of Acidic Residues in Helices TH8–TH9 in Membrane Interactions of the Diphtheria Toxin T Domain. Toxins. 2015;7(4):1303-23.

Rolf JM, Gaudin HM, Eidels L. Journal of Biological Chemistry. 1990;265(13):7331-7.

Louie GV, Yang W, Bowman ME, Choe S. Molecular cell. 1997;1(1):67-78.

Mitamura T, Umata T, Nakano F, Shishido Y, Toyoda T, Itai A, et al. Journal of Biological Chemistry. 1997; 272(43):27084-90.

Hooper KP, Eidels L. Biochemical and biophysical research communications. 1996;220(3):675-80.

Shen WH, Choe S, Eisenberg D, Collier RJ. Journal of Biological Chemistry. 1994;269(46):29077-84.

Greenfield L, Johnson VG, Youle RJ. Science. 1987;238(4826):536-9.

Montecucco C, Schiavo G, Tomasi M. Biochem J. 1985;231:123-8.

Chung DW, Collier RJ. Biochimica et Biophysica Acta (BBA)-Enzymology. 1977;483(2):248-57.

Makarov DE, Keller CA, Plaxco KW, Metiu H. Proceedings of the National Academy of Sciences. 2002;99(6):3535-9.

Galzitskaya OV, Reifsnyder DC, Bogatyreva NS, Ivankov DN, Garbuzynskiy SO. Proteins: Structure, Function, and Bioinformatics. 2008;70(2):329-32.

Tsai C-J, Nussinov R. Protein science: a publication of the Protein Society. 1997;6(7):1426.

Hong L, Lei J. Journal of Polymer Science Part B: Polymer Physics. 2009;47(2):207-14.

Cohen FE, Sternberg MJ. Journal of molecular biology. 1980;138(2):321-33.

Kumar A, Purohit R. Gene. 2012;511(1):125-6.

Kabsch W, Sander C. Biopolymers. 1983;22(12):2577-637.

Entomology and Applied Science Letters is an international peer reviewed publication which publishes scientific research & review articles related to insects that contain information of interest to a wider audience, e.g. papers bearing on the theoretical, genetic, agricultural, medical and biodiversity issues. Emphasis is also placed on the selection of comprehensive, revisionary or integrated systematics studies of broader biological or zoogeographical relevance. Papers on non-insect groups are no longer accepted. In addition to full-length research articles and reviews, the journal publishes interpretive articles in a Forum section, Short Communications, and Letters to the Editor. The journal publishes reports on all phases of medical entomology and medical acarology, including the systematics and biology of insects, acarines, and other arthropods of public health and veterinary significance.
Issue 2 Volume 7 - 2020
Call for Papers
Entomology and Applied Science Letters supports the submission of entomological papers that contain information of interest to a wider reader groups e. g. papers bearing on taxonomy, phylogeny, biodiversity, ecology, systematic, agriculture, morphology. The selection of comprehensive, revisionary or integrated systematics studies of broader biological or zoogeographical relevance is also important. Distinguished entomologists drawn from different parts of the world serve as honorary members of the Editorial Board. The journal encompasses all the varied aspects of entomological research. This has become the need felt in scientific research due to the emphasis on intra-, inter-, and multi-disciplinary approach.