Advertisement

Structural Analyses of the Mode of Binding Between AANAT Protein with 14-3-3 Protein Involved in Human Melatonin Synthesis

  • Ananya Ali
  • Sanchari Bhattacharjee
  • Angshuman Bagchi
Conference paper
Part of the Advances in Intelligent Systems and Computing book series (AISC, volume 340)

Abstract

Arylalkylamine N-acetyltransferase (AANAT) or Serotonin N-acetyltransferase is one of the key enzymes for the synthesis of melatonin in humans. In the process, the regular binding partner of this AANAT protein is 14-3-3 protein. A mutation of A129T in the AANAT protein leads to decreased functionality of the AANAT protein. So far the mechanistic details of this loss of binding have not been elucidated. In the present work, we tried to utilize structural bioinformatic approach to understand the differences in pattern of bindings between AANAT wild type and mutant forms. We used molecular mechanics calculations to describe the interactions of wild type and mutant AANAT proteins with its binding partner 14-3-3 proteins. So far, this is the first report that characterizes the difference in binding between the two forms of the protein. Therefore, the results from this study may be useful for the development of drugs in patients having impaired melatonin synthesis.

Keywords

Protein-protein interaction Arylalkylamine N-acetyltransferase Molecular modeling Molecular mechanics Mutations 

Notes

Acknowledgment

The authors would like to thank the DST-PURSE program 2012-2015 going on in the Department of Biochemistry and Biophysics, University of Kalyani for providing different instrumental and infrastructural support. The authors are also thankful to the DBT sponsored Bioinformatics Infrastructure Facility in the Department of Bio-chemistry and Biophysics, University of Kalyani for the necessary support.

References

  1. 1.
    Bagchi, A., Mortb, M., Lic, B., Xind, F., Carlisec, C., Oronc, T., Powellc, C., Youne, E., Radivojacd, P., Cooperb, D.N., Mooneyc, S.D.: Analysis of features from protein-protein hetero-complex structures to predict protein interaction interfaces using machine learning: CIMTA. Procedia Technol. 10, 62–66 (2013)CrossRefGoogle Scholar
  2. 2.
    Ganguly, S., Weller, J.L., Ho, A., Chemineau, P., Malpaux, B., Klein, D.C.: Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc. Natl. Acad. Sci. USA 102(4), 1222–1227 (2005)CrossRefGoogle Scholar
  3. 3.
    Hickman, A.B., Klein, D.C., Dyda, F.: Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 Å resolution suggests a catalytic mechanism. Mol. Cell 1, 23–32 (1999)CrossRefGoogle Scholar
  4. 4.
    Blomeke, B., Golka, K., Griefahn, B., Roemer, H.C.: Arylalkylamine N-acetyltransferase (AANAT) genotype as a personal trait in melatonin synthesis. J. Toxicol Environ. Health A 71(13–14), 874–876 (2008)CrossRefGoogle Scholar
  5. 5.
    Bijlenga, D., Van Someren, E.J., Gruber, R., Bron, T.I., Kruithof, I.F., Spanbroek, E.C., Kooij, J.J.: Body temperature, activity and melatonin profiles in adults with attention-deficit/hyperactivity disorder and delayed sleep: a case-control study. J. Sleep Res. 6, 607–616 (2013)CrossRefGoogle Scholar
  6. 6.
    Fu, H., Subramanian, R.R., Masters, S.C.: 14-3-3 PROTEINS: structure, function, and regulation. Ann. Rev. Pharmacol. Toxicol. 40, 617–647 (2000)CrossRefGoogle Scholar
  7. 7.
  8. 8.
  9. 9.
    Wolf, E., De Angelis, J., Khalil, E.M., Cole, P.A., Burley, S.K.: X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition. J. Mol. Biol. 317(2), 215–224 (2002)CrossRefGoogle Scholar
  10. 10.
    Choong, Y.S., Tye, G.J., Lim, T.S.: Minireview: applied structural bioinformatics in proteomics. Protein J. 32, 505–511 (2013)CrossRefGoogle Scholar
  11. 11.
    Cukuroglu, E., Engin, E.H., Gursoy, A., Keskin, O.: Hot spots in protein-protein interfaces: towards drug discovery. Prog. Biophys. Mol. Biol., 1–9 (2014)Google Scholar
  12. 12.
    Rao, S.V., Srinivas, K., Sujini, G.N., Sunand Kumar, G.N.: Protein-protein interaction detection: methods and analysis. Int. J. Proteomics 2014, Article ID 147648 (2014)Google Scholar
  13. 13.
    Sudha, G., Nussinov, R., Srinivasan, N.: An overview of recent advances in structural bioinformatics of protein-protein interactions and a guide to their principles. Prog. Biophys. Mol. Biol. 116(2), 141–150 (2014)CrossRefGoogle Scholar

Copyright information

© Springer India 2015

Authors and Affiliations

  • Ananya Ali
    • 1
  • Sanchari Bhattacharjee
    • 1
  • Angshuman Bagchi
    • 1
  1. 1.Department of Biochemistry and BiophysicsUniversity of KalyaniKalyani, NadiaIndia

Personalised recommendations