Title

Authors

Panneer Selvam Suresh¹, Olujide Olubiyi², Chinnasamy Thirunavukkarasu³, Birgit Strodel², Muthuvel Suresh Kumar¹* 

Affiliation

¹Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry, India; ²Institute of Structural Biology and Biophysics / ISB-3, Research Centre Julich, 52425 Julich, Germany; ³Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry, India 

Email

suresh.bic@pondiuni.edu.in; *Corresponding author

Phone

+91 413 2655583

Fax

+91 413 2655211

Article Type

Hypothesis

Date

Received March 01, 2011; Accepted March 16, 2011; Published March 26, 2011

Alkaline sphingomyelinase, which is expressed in the human intestine and hydrolyses sphingomyelin, is a component of the plasma and the lysosomal membranes. Hydrolase of sphingomyelin generates ceramide, sphingosine, and sphingosine 1-phosphate that have regulatory effects on vital cellular functions such as proliferation, differentiation, and apoptosis. The enzyme belongs to the Nucleotide Pyrophosphatase/Phosphodiesterase family and it differs in structural similarity with acidic and neutral sphingomyelinase. In the present study we modeled alkaline sphingomyelinase using homology modeling based on the structure of Nucleotide Pyrophosphatase/Phosphodiesterase from Xanthomonas axonopodis with which it shares 34% identity. Homology modeling was performed using Modeller9v7. We found that Cys78 and Cys394 form a disulphide bond. Further analysis shows that Ser76 may be important for the function of this enzyme, which is supported by the findings of Wu et al. (2005), that S76F abolishes the activity completely. We found that the residues bound to Zn2+ are conserved and geometrically similar with the template. Molecular Dynamics simulations were carried out for the modeled protein to observe the effect of Zinc metal ions. It was observed that the metal ion has little effect with regard to the stability but induces increased fluctuations in the protein. These analyses showed that Zinc ions play an important role in stabilizing the secondary structure and in maintaining the compactness of the active site.  

Keywords

alkaline sphingomyelinase; homology modeling, NPP; gromacs

Citation

Suresh et al. Bioinformation 6(2): 78-82 (2011)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.