Characterization of structural and functional role of selenocysteine in selenoprotein H and its impact on DNA binding
- 405 Downloads
Selenoproteins are a group of proteins which contain selenocysteine (Sec or U) in their primary structure. Selenoproteins play a critical role in antioxidant defense, hormone metabolism, immune responses and muscle development. The selenoprotein H (SELENOH) is essential in the regulation of gene expression in response to redox status and antioxidant defense. It has Sec residue located in conserved CXXU motif similar to other selenoproteins. However, exact biological function of Sec residue in SELENOH is not known in detail. Therefore, it is essential to understand the structural and functional role of Sec in SELENOH. In the present study, homology modelling and MD simulation were performed to understand the role of Sec residue in SELENOH. The modelled 3D structure of wild-SELENOH along with two mutants (Mut-U44C and Mut-41CS–SC44) was subjected to MD simulation. Based on simulation results, we demonstrate that wild-SELENOH structure is dynamically stabilized by network of intramolecular hydrogen bonding and internal residue contacts facilitated by Sec residue. In contrast, notable differences have been observed in residue contacts and stability in other two mutant structures. Additionally, docking studies revealed that 3PRGRKRK9 motif of wild-SELENOH interacts with HSE and STRE of DNA molecule as observed experimentally. Similar to earlier reports, our sequence analysis study pinpoints conserved 3PRGRKRK9 motif present in SELENOH perform dual role as AT-hook motif and NLS. Overall, the obtained results clearly illustrate Sec residue plays an important role to restore functionally active conformation of SELENOH. The present study broadened our current understanding regarding the role of selenocysteine in protein structure and function.
KeywordsSelenocysteine Selenoprotein H MD simulation Molecular docking DNA binding
SHB gratefully acknowledges DST-SERB for providing research grant under young scientist scheme (YSS/2015/0001030). The authors are thankful to Bioinformatics Centre, Savitribai Phule Pune University, Pune for infrastructure support.
Compliance with ethical standards
Conflict of interest
The authors declare that they do not have any conflict of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
- Dassault Systèmes BIOVIA (2016) Discovery Studio, v18.104.22.16843, San Diego: Dassault SystèmesGoogle Scholar
- Dikiy AA, Novoselov SV, Fomenko DE, Sengupta A, Carlson BA, Cerny RL, Ginalski K, Grishin NV, Hatfield DL, Gladyshev VN (2007) SelT, SelW, SELENOH, and Rdx12: genomics and molecular insights into the functions of selenoproteins of a novel thioredoxin-like family. Biochemistry 46:6871–6882CrossRefPubMedGoogle Scholar
- Dokudovskaya S, Waharte F, Schlessinger A, Pieper U, Devos DP, Cristea IM, Williams R, Salamero J, Chait BT, Sali A, Field MC, Rout MP, Dargemont C (2011) A Conserved coatomer-related complex containing Sec13 and Seh1 dynamically associates with the vacuole in Saccharomyces Cerevisiae. Mol Cell Proteom 10(M110):006478. https://doi.org/10.1074/mcp.m110.006478 Google Scholar
- Flohe L (1989) In g1utathione: chemical, biochemical and medical aspects. In: Poulson R, Avamovie O, Dolphin D (eds) Cell Biochemistry and function. Wiley, New York, pp 644–731Google Scholar
- Lee S-R, Bar-Noy S, Kwon J, Levine RL, Stadtman TC, Rhee SG (2000) Mammalian thioredoxin reductase: oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity. Proc Natl Acad Sci USA 97:2521–2526CrossRefPubMedPubMedCentralGoogle Scholar
- Mohamadi M, Ebrahimipour SY, Castro J, Torkzadeh-Mahani M (2016) Synthesis, characterization, crystal structure, DNA and BSA binding, molecular docking and in vitro anticancer activities of a mononuclear dioxido-uranium(VI) complex derived from a tridentate ONO aroylhydrazone. J Photochem Photobiol B 158:219–227. https://doi.org/10.1016/j.jphotobiol.2016.03.001 CrossRefPubMedGoogle Scholar
- Pierri CL, Parisi G, Porcelli V (2010) Computational approaches for protein function prediction: a combined strategy from multiple sequence alignment to molecular docking-based virtual screening. Biochim Biophys Acta 1804:1695–1712. https://doi.org/10.1016/j.bbapap.2010.04.008 CrossRefPubMedGoogle Scholar