Are Pro8/Pro18 really critical for functional dynamic behavior of human endostatin N-terminal peptide? A comparative molecular dynamics study
- 108 Downloads
- 2 Citations
Abstract
Endostatin which is derived from the non-collagenous domain 1 of collagen XVIII and is a recently identified broad spectrum anti-angiogenesis agent, inhibits 65 different tumor types. The N-terminal fragment of endostatin protein (ES) has the same antitumor, antimigration and antipermeability effects as the entire protein. In the current study, we modeled two mutant variants of ES with two mutation sites (M1-ES (Pro8 → Ala) and M2-ES (Pro18 → Ala)) and tried to understand proline’s effect on the peptide structure/stability by introducing P8A/P18A mutations, and then in order to gain functional insight into mutation caused by amino acid substitution to the peptide structure/function, these effects were predicted using computational tools. From the RMSD analyses, it can be concluded that dynamic behavior of wild-type and mutant structures was not significantly different from each other and all systems reached equilibrium. The RMSF analysis also revealed that the M2-ES has smaller overall flexibility than the WT-ES and M1-ES structures. The radius of gyration analysis then confirmed the structure of M2-ES compared to wild-type and M1 variant becomes more compact during simulation of our systems. Finally, molecular dynamics simulation analysis shows that replacement of Pro residue with Ala is able to induce a distinct β-sheet in both mutant structures. Indeed, the docking analysis shows the WT-ES and M2-ES bind to the same region of αvβ3 integrin, suggesting similar interaction pattern with a relatively equal binding energy into this receptor. Our results speculated that the P8A/P18A replacements confer no improvement (or no tangible weakness) in the peptide biological activity although is able to change structural conformation of N-terminal fragment of human endostatin protein.
Keywords
Proline Endostatin MD simulation Molecular dockingNotes
Acknowledgements
We thank the Research Council of Kermanshah University of Medical Sciences (KUMS) for financial support of this investigation (Grant No. 95303). We specially thank Mrs. Shirin Valizadeh for her gracious helps in the time of reviewing and revising of this article. Effective, instructive and invaluable comments provided by the respectful editor and anonymous reviewers are gratefully acknowledged.
Compliance with ethical standards
Conflict of interest
Authors certify that no actual or potential conflict of interest in relation to this article exists.
References
- 1.H. Rasouli, S. Parvaneh, A. Mahnam, M. Rastegari-Pouyani, Z. Hoseinkhani, K. Mansouri, Int. J. Biol. Macromol. 96, 118–128 (2017)CrossRefGoogle Scholar
- 2.H. Rasouli, L. Mahamed-Khosroushahi, K. Mansouri, J. Rep. Pharm. Sci. 3, 17–18 (2014)Google Scholar
- 3.K. Mansouri, A. Mostafie, D. Rezazadeh, M. Shahlaei, M.H. Modarressi, Hum. Mol. Genet. 25, 233–244 (2016)CrossRefGoogle Scholar
- 4.S. Pieraccini, M. Sironi, P. Francescato, G. Speranza, L.M. Vicentini, P. Manitto, Phys. Chem. Chem. Phys. 8, 3066 (2006)CrossRefGoogle Scholar
- 5.D. Hanahan, J. Folkman, Cell 86, 353 (1996)CrossRefGoogle Scholar
- 6.X. Qi, Y. Liu, W. Wei, X. Huang, Y. Zuo, Biomed. Rep. 1, 761 (2013)Google Scholar
- 7.P.H.M. Torres, G.L.S.C. Sousa, P.G. Pascutti, Proteins 79, 2684 (2011)CrossRefGoogle Scholar
- 8.M. Shichiri, Y. Hirata, FASEB J. 15, 1044 (2001)CrossRefGoogle Scholar
- 9.S. Tjin Tham, Robert M. Satchi-Fainaro, A.E.B. Ronit, V.M.S. Ramanujam, J. Folkman, K. Javaherian, Cancer Res. 65, 3656 (2005)CrossRefGoogle Scholar
- 10.M.G. Cattaneo, S. Pola, P. Francescato, F. Chillemi, L.M. Vicentini, Exp. Cell Res. 283, 230 (2003)CrossRefGoogle Scholar
- 11.M.P. Williamson, Biochem. J. 297, 249 (1994)CrossRefGoogle Scholar
- 12.A.A. Morgan, E. Rubenstein, PLoS ONE 8, e53785 (2013)CrossRefGoogle Scholar
- 13.H. Yamaguchi, J.N. Muth, M. Varadi, A. Schwartz, G. Varadi, Proc. Natl. Acad. Sci. USA 96, 1357 (1999)CrossRefGoogle Scholar
- 14.M.W. MacArthur, J.M. Thornton, J. Mol. Biol. 218, 397 (1991)CrossRefGoogle Scholar
- 15.M. Levitt, J. Mol. Biol. 145, 251 (1981)CrossRefGoogle Scholar
- 16.C. M Deber, B. Brodsky, A. Rath, eLS, 1 (2010)Google Scholar
- 17.D.J.A. Roderer, M.A. Schärer, M. Rubini, R. Glockshuber, Nature 5, 11840 (2015)Google Scholar
- 18.X. Robert, P. Gouet, Nucleic Acids Res. 42, W320 (2014)CrossRefGoogle Scholar
- 19.M. Mehrabi, R. Khodarahmi, M. Shahlaei, J. Biomol. Struct. Dyn. 21, 1–60 (2016). [Epub ahead of print] Google Scholar
- 20.R. De Paris, C.V. Quevedo, D.D. Ruiz, O.N. de Souza, R.C. Barros, Comput. Intell. Neurosci. 15, 1 (2015)CrossRefGoogle Scholar
- 21.Y.-H. Ding, K. Javaherian, K.-M. Lo, R. Chopra, T. Boehm, J. Lanciotti, B.A. Harris, Y. Li, R. Shapiro, E. Hohenester, R. Timpl, J. Folkman, D.C. Wiley, Proc. Natl. Acad. Sci. USA 95, 10443 (1998)CrossRefGoogle Scholar
- 22.A. Fiser, R.K. Do, A. Sali, Protein Sci. 9, 1753 (2000)CrossRefGoogle Scholar
- 23.G. Ratnavali, N. Devi, K. Sri, J. Raju, B. Sirisha, R. Kavitha, Ann. Biol. Res. 2, 114 (2011)Google Scholar
- 24.N. Eswar, D. Eramian, B. Webb, MY. Shen, A. Sali, Methods Mol Biol. 426, 145 (2008)CrossRefGoogle Scholar
- 25.R.A. Laskowski, M.W. MacArthur, D.S. Moss, J.M. Thornton, J. Appl. Crystallogr. 26, 283 (1993)CrossRefGoogle Scholar
- 26.C. Colovos, T.O. Yeates, Protein Sci. 2, 1511 (1993)CrossRefGoogle Scholar
- 27.B. Hess, J. Chem. Theory Comput. 4, 116 (2008)CrossRefGoogle Scholar
- 28.G. Bussi, D. Donadio, M. Parrinello, J. Chem. Phys. 126, 1 (2007)CrossRefGoogle Scholar
- 29.M. Parrinello, A. Rahman, J. Appl. Phys. 52, 7182 (1981)CrossRefGoogle Scholar
- 30.T. Darden, D. York, L. Pedersen, J. Chem. Phys. 98, 10089 (1993)CrossRefGoogle Scholar
- 31.D.E. Tanner, K.-Y. Chan. J. C. Phillips, K. Schulten. J. Chem. Theory Comput. 7, 3635 (2011)CrossRefGoogle Scholar
- 32.M.Ø. Jensen, T.R. Jensen, K. Kjaer, T. Bjørnholm, O.G. Mouritsen, G.H. Peters, Biophys. J. 83, 98 (2002)CrossRefGoogle Scholar
- 33.M. Shahlaei, B. Rahimi, M.R. Ashrafi-Koosh, K. Sadrjavadi, R. Khodarahmi, J. Lumin. 158, 91 (2015)CrossRefGoogle Scholar
- 34.W. Kabsch, C. Sander, Biopolymers 22, 2577 (1983)CrossRefGoogle Scholar
- 35.T.J. Dolinsky, P. Czodrowski, H. Li, J.E. Nielsen, G. Klebe, N.A. Baker, Nucleic Acids Res. 35, W522 (2007)CrossRefGoogle Scholar
- 36.N.A. Baker, D. Sept, S. Joseph, M.J. Holst, J.A. McCammon, Proc. Natl. Acad. Sci. USA 98, 10037 (2001)CrossRefGoogle Scholar
- 37.K. Lee, Int. J. Mol. Sci. 9, 65 (2008)CrossRefGoogle Scholar
- 38.H. Rasouli, S. Hosseini-Ghazvini, H.R. Adibi, Khodarahmi, Food Funct. 1 (2017)Google Scholar
- 39.J.B. Ghasemi, E. Nazarshodeh, H. Abedi, J. Iran Chem. Soc. 12, 1789 (2015)CrossRefGoogle Scholar
- 40.S.R. Comeau, D.W. Gatchell, S. Vajda, C.J. Camacho, Bioinformatics 20, 45 (2004)CrossRefGoogle Scholar
- 41.A. Rakhmetov, S.P. Lee, D. Grebinyk, L. Ostapchenko, H.Z. Chae, J. Appl. Pharm. Sci. 5, 8011 (2015)Google Scholar
- 42.J.-P. Xiong, B. Mahalingham, J.L. Alonso, L.A. Borrelli, X. Rui, S. Anand, B.T. Hyman, T. Rysiok, D. Müller-Pompalla, S.L. Goodman, M.A. Arnaout, J. Cell Biol. 186, 589 (2009)CrossRefGoogle Scholar
- 43.R.A. Laskowski, Nucleic Acids Res. 29, 221 (2001)CrossRefGoogle Scholar
- 44.A. Elengoe, M. Abu Naser, S. Hamdan, Int. J. Mol. Sci. 15, 6797 (2014)CrossRefGoogle Scholar
- 45.U.B. Sonavane, S.K. Ramadugu, R.R. Joshi, J. Biomol. Struct. Dyn. 26, 203 (2008)CrossRefGoogle Scholar
- 46.M. Sekijima, C. Motono, S. Yamasaki, K. Kaneko, Y. Akiyama, Biophys. J. 85, 1176 (2003)CrossRefGoogle Scholar
- 47.D. van der Spoel, H.J. Vogel, H.J.C. Berendsen, Proteins Struct. Funct. Genet. 24, 450 (1996)CrossRefGoogle Scholar
- 48.N.S.F. Mazlan, N.B.A. Khairudin, J. Biomol. Struct. Dyn. 34, 1486 (2015)CrossRefGoogle Scholar
- 49.M.Y. Lobanov, N.S. Bogatyreva, O.V. Galzitskaya, Mol. Biol. 42, 623 (2008)CrossRefGoogle Scholar
- 50.H.-L. Liu, Y.-C. Wu, J.-H. Zhao, H.-W. Fang, Y. Ho, J. Biomol. Struct. Dyn. 24, 229 (2006)CrossRefGoogle Scholar
- 51.S. Dalal, A. Mhashal, N. Kadoo, S.M. Gaikwad, J. Biomol. Struct. Dyn. 35, 330 (2016)CrossRefGoogle Scholar
- 52.R.E. Hubbard, K.H. Muhammad, Encyclopedia of Life Sciences (Wiley, Chichester, 2010)Google Scholar
- 53.S. Stahl, S. Gaetzner, T.D. Mueller, U. Felbor, Genes Cells 10, 929 (2005)CrossRefGoogle Scholar
- 54.P.K. Weiner, R. Langridge, J.M. Blaney, R. Schaefer, P.A. Kollman, Proc. Natl. Acad. Sci. USA 79, 3754 (1982)CrossRefGoogle Scholar
- 55.C. Carvalho, D. Vlachakis, G. Tsiliki, V. Megalooikonomou, S. Kossida, Peer J. 1, e185 (2013)CrossRefGoogle Scholar
- 56.A.-B. H. Mekky. H. G. Elhaes. M. M. El-Okr, M. A. Ibrahim, J. Nanomater. Mol. Nanotechnol. 2015 (2015)Google Scholar
- 57.Z. Zhe, W. Shawn, A. Emil, Phys. Biol. 8, 035001 (2011)CrossRefGoogle Scholar
- 58.X.-Y. Meng, H.-X. Zhang, M. Mezei, M. Cui, Curr. Comput. Aided Drug Des. 7, 146 (2011)CrossRefGoogle Scholar
- 59.B.J. McConkey, V. Sobolev, M. Edelman, Curr. Sci. 83, 845 (2002)Google Scholar
- 60.R.C. Turaga, L. Yin, J.J. Yang, H. Lee, I. Ivanov, C. Yan, H. Yang, H.E. Grossniklaus, S. Wang, C. Ma, L. Sun, R. Liu, Nature 7, 11675 (2016)Google Scholar
- 61.R.O. Hynes, Cell 110, 673 (2002)CrossRefGoogle Scholar
- 62.R. Chamani, S.M. Asghari, A.M. Alizadeh, K. Mansouri, T. Doroudi, P.H. Kolivand, H. Ghafouri, S. Ehtesham, H. Rabouti, F. Mehrnejad, Biochim. Biophys. Acta (BBA)-Proteins Proteom. 1864, 1765 (2016)CrossRefGoogle Scholar
- 63.R. Chamani, S.M. Asghari, A.M. Alizadeh, S. Eskandari, K. Mansouri, R. Khodarahmi, M. Taghdir, Z. Heidari, A. Gorji, A. Aliakbar, B. Ranjbar, K. Khajeh, Vasc. Pharmacol. 72, 73 (2016)CrossRefGoogle Scholar
- 64.C. Faye, C. Moreau, E. Chautard, R. Jetne, N. Fukai, F. Ruggiero, M.J. Humphries, B.R. Olsen, S. Ricard-Blum, J. Biol. Chem. 284, 22029 (2009)CrossRefGoogle Scholar
- 65.N.M. Pandya, N.S. Dhalla, D.D. Santani, Vasc. Pharmacol. 44, 265 (2006)CrossRefGoogle Scholar
- 66.N. Yamaguchi, B. Anand-Apte, M. Lee, T. Sasaki, N. Fukai, R. Shapiro, I. Que, C. Lowik, R. Timpl, B. Oslen, EMBO J. 18, 4414 (1999)CrossRefGoogle Scholar
- 67.S.A. Wickström, K. Alitalo, J. Keski-Oja, Adv. Cancer Res. 94, 197 (2005)CrossRefGoogle Scholar
- 68.M.S. O’Reilly, T. Boehm, Y. Shing, N. Fukai, G. Vasios, W.S. Lane, E. Flynn, J.R. Birkhead, B.R. Olsen, J. Folkman, Cell 88, 277 (1997)CrossRefGoogle Scholar
- 69.S.A. Wickström, K. Alitalo, J. Keski-Oja, J. Biol. Chem. 279, 20178 (2004)CrossRefGoogle Scholar
- 70.M. Rehn, T. Veikkola, E. Kukk-Valdre, H. Nakamura, M. Ilmonen, C.R. Lombardo, T. Pihlajaniemi, K. Alitalo, K. Vuori, Proc. Natl. Acad. Sci. USA 98, 1024 (2001)CrossRefGoogle Scholar
- 71.A.K. Olsson, I. Johansson, H. Åkerud, B. Einarsson, R. Christofferson, T. Sasaki, R. Timpl, L. Claesson-Welsh, Cancer Res. 64, 9012 (2004)CrossRefGoogle Scholar
- 72.S.P. Balasubramanian, S.S. Cross, J. Globe, A. Cox, N.J. Brown, M.W. Reed, BMC Cancer 7, 1 (2007)CrossRefGoogle Scholar
- 73.A. Abdollahi, L. Hlatky, P.E. Huber, Drug Resist. Update 8, 59 (2005)CrossRefGoogle Scholar
- 74.A. Kolozsi, A. Jancsó, N.V. Nagy, T. Gajda, J. Inorg. Biochem. 103, 940 (2009)CrossRefGoogle Scholar
- 75.K. Javaherian, T.-Y. Lee, R.M. Tjin Tham Sjin, D.E. Parris, L. Hlatky, Dose Response 9, 369 (2011)CrossRefGoogle Scholar
- 76.A.M. Thayer, Chem. Eng. News 89, 13 (2011)Google Scholar
- 77.C. Borghouts, C. Kunz, B. Groner, J. Pept. Sci. 11, 713 (2005)CrossRefGoogle Scholar
- 78.A. Zambrowicz, M. Timmer, A. Polanowski, G. Lubec, T. Trziszka, Amino Acids 44, 315 (2013)CrossRefGoogle Scholar
- 79.J. Thundimadathil, J. Amino Acids 2012, 1 (2012)CrossRefGoogle Scholar
- 80.C.G.P. Doss, B. Rajith, N. Garwasis, P.R. Mathew, A.S. Raju, K. Apoorva, D. William, N. Sadhana, T. Himani, I. Dike, Appl. Transl. Genom. 1, 37 (2012)CrossRefGoogle Scholar
- 81.M. Hacke, T. Gruber, C. Schulenburg, J. Balbach, U. Arnold, FEBS J. 280, 4454 (2013)CrossRefGoogle Scholar
- 82.A.K. Jha, A. Colubri, M.H. Zaman, S. Koide, T.R. Sosnick, K.F. Freed, Biochemistry 44, 9691 (2005)CrossRefGoogle Scholar
- 83.V. Vieille, G.J. Zeikus, Microbiol. Mol. Biol. Rev. 65, 1 (2001)CrossRefGoogle Scholar
- 84.W.J. Wedemeyer, E. Welker, H.A. Scheraga, Biochemistry 41, 14637 (2002)CrossRefGoogle Scholar
- 85.T.F. Huang, Cell. Mol. Life Sci. 54, 527 (1998)CrossRefGoogle Scholar
- 86.L.A. Calderon, J.C. Sobrinho, D.K. Zaqueo, A.A. De Moura, A.N. Grabner, M.V. Mazzi, S. Marcussi, A. Nomizo, C.F.C. Fernandes, J.P. Zuliani, B.M.N. Carvalho, S.L. da Silva, R.G. Stábeli, A.M. Soares, BioMed. Res. Int. 1, 1 (2014)CrossRefGoogle Scholar
- 87.Z. Liu, F. Wang, X. Chen, Drug Dev. Res. 69, 329 (2008)CrossRefGoogle Scholar