Title

Structure modeling and inhibitor prediction of NADP oxidoreductase enzyme from Methanobrevibacter smithii 

Authors

Ashwani Sharma^{1, 2}, Prem Prashant Chaudhary¹*, Sunil Kumar Sirohi^{1, 3}, Jyoti Saxena^{1, 4}

Affiliation

¹Bioroutes Life Sciences, SCO No-401, IInd Floor, Mugal Canal, Karnal-132001, Haryana, India; ²Center of Drug Discovery Research, NewEraProteomics, C-1/31, Yamuna Vihar, New Delhi-110053, India; ³Nutrition Biotechnology Lab, Animal Biotechnology Centre, National Dairy Research Institute, Karnal -132001, Haryana, India; ⁴Department of Biosciences and Biotechnology, Banasthali University, Rajasthan-304022, India 

Email

luckypgi@gmail.com; *Corresponding author

Phone

+91-9896984104

Fax

0184-2250042

Article Type

Hypothesis

Date

Received January 30, 2011; Accepted February 17, 2011; Published March 02, 2011

The F420-dependent NADP oxidoreductase enzyme from Methanobrevibacter smithii catalyzes the important electron transfer step during methanogenesis. Therefore, it may act as potential target for blocking the process of methane formation. Its protein sequence is available in GenBank (accession number: ABQ86254.1) however no report has been found about its 3D protein structure. In this work, we first time claim 3D model structure of F420-dependent NADP oxidoreductase enzyme from Methanobrevibacter smithii by comparative homology modeling method. Swiss model and ESyPred3d (via Modeller 6v2) software’s were generated the 3D model by detecting 1JAX (A) as template along with sequence identities of 34.272% and 35.40%. Furthermore, PROCHECK with Ramachandran plot and ProSA analysis revealed that swiss model produced better model than Modeller6v2 with 98.90% of residues in favored and additional allowed regions (RM plot) as well as with ProSA Z score of -7.26. In addition, we investigated that the substrate F420 bound at the cavity of the model. Subsequently, inhibitor prediction study revealed that Lovastatin (-22.07 Kcal/mol) and Compactin (Mevastatin) (-21.91 Kcal/mol) produced more affinity for model structure of NADP oxidoreducatse as compared to F420 (-14.40 Kcal/mol). It indicates that the Lovastatin and Compactin (Mevastatin) compounds (Negative regulator) may act as potential inhibitor of F420 dependent NADP oxidoreducatse protein.  

Keywords

Methanogenesis, Homology modeling, Functional site prediction, Substrate finding, Oxidoreductase Inhibitor, Docking, Autodock

Citation

Sharma et al. Bioinformation 6(1): 15-19 (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.