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Title

 

 

 

 

Structure based prediction of functional sites with potential Inhibitors to Nudix enzymes from disease causing microbes 

Authors

Ashwani Sharma1, Ashish Vijay Tendulkar2, Pramod Prabhakar Wangikar3*

Affiliation

1Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai- 400 076, Maharashtra, India; 2Department of Computer Science and Engineering, Indian Institute of Technology Madras, Chennai- 600036, India; 3Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai- 400076, Maharashtra, India 

Email

wangikar@iitb.ac.in

Phone

+91 22 2576 7232

Article Type

Hypothesis

 

Date

Received November 30, 2010; Accepted December 30, 2010; Published January 22, 2011
 

Abstract

The functional sites were predicted for Nudix enzymes from pathogenic microorganisms such as Streprococcus pneumonia (2B06) and Enterococcus faecalis (2AZW). Their structures are already determined, however, no data is reported about their functional sites, substrates and inhibitors. Therefore, we report prediction of functional sites in these Nudix enzymes via Geometric Invariant (GI) technique (Construct different geometries of peptides which remain unchanged). The GI method enumerated 2B06: RA57, EA58, EA61, EA62 and 2AZW: RA62, EA63, EA66, EA67 as putative functional sites in these Nudix enzymes. In addition, the substrate was predicted via Molecular docking (Docking of substrates against whole structure of Nudix enzymes). The substrate ADP-Ribose was docked with the Nudix enzymes, 2B06 (Docking energy -15.68 Kcal/mol) and 2AZW (Docking energy -10.86 Kcal/mol) with the higher affinity and the lower docking energy as compared to other substrates. The residues EA62 in 2B06 and RA62 in 2AZW make hydrogen bonds with the ADP-ribose. Furthermore, we screened 51 inhibitor compounds against structures of 2B06 and 2AZW. The inhibitor compounds AMPCPR and CID14258187 were docked well as compared to other compounds. The compound CID14258187 was also in agreement with Lipinski rule of 5 for drug likeness properties. Therefore, our findings of functional sites, substrates and inhibitors for these Nudix enzymes may help in structure based drug designing against Streprococcus pneumonia and Enterococcus faecalis. 

Keywords

 

Functional sites, Nudix proteins, SG target proteins, substructures, Molecular Docking, Geometric Invariant. 

Citation

Sharma et al. Bioinformation 5(8): 341-349 (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.