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

Sharma A, Tendulkar AV, Wangikar PP - Bioinformation (2011)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

It shows the distribution of the Nudix inhibitors based on their docking score against the whole structure of the 2B06 and 2AZW Nudix enzymes. The inhibitors AMPCPR and CID14258187 show more affinity for (a) the 2B06 with score of 5292 and 4888 and (b) for 2AZW with higher docking score of 4902 and 4268. The docking is performed by Patchdock software.
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Figure 5: It shows the distribution of the Nudix inhibitors based on their docking score against the whole structure of the 2B06 and 2AZW Nudix enzymes. The inhibitors AMPCPR and CID14258187 show more affinity for (a) the 2B06 with score of 5292 and 4888 and (b) for 2AZW with higher docking score of 4902 and 4268. The docking is performed by Patchdock software.

Mentions: Docking of 51 inhibitor compounds revealed that the compounds AMPCPR and CID14258187 show more affinity for the 2B06 and 2AZW as compared to other inhibitor compounds. The compound AMPCPR is produced Patchdock score of 5292 and CID14258187 of 4888 in case of 2B06, which is higher than other compounds (Figure 5(a)) (Table 6 see supplementary material) On the other hand for 2AZW, AMPCPR produced score of 4902 and CID14258187 of 4268 (Figure 5(b)). The compounds AMPCPR and CID14258187 bind within the binding site pockets of these Nudix enzymes and surround by RA57, EA62 ,EA58 (2B06) and RA62, EA63, EA66, EA67 (2AZW) binding sites residues (Figure 4). Furthermore, drug likeness properties analyses revealed that the compound CID14258187 shows no violation for the Lipinski rule of 5 (rules for selecting a compound as a potential drug) (Table 4 see supplementary material). On the other hand, the compound AMPCPR is not in agreement of rule of 5 (Table 4 see supplementary material).Therefore, we predict CID14258187 (2R, 3R, 4S, 5R)-2-(6-aminopurin-9-yl)-5-(dichlorophosphoryloxymethyl) oxolane-3, 4-diol) as potential inhibitor of the Nudix enzymes 2B06 and 2AZW.


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

Sharma A, Tendulkar AV, Wangikar PP - Bioinformation (2011)

It shows the distribution of the Nudix inhibitors based on their docking score against the whole structure of the 2B06 and 2AZW Nudix enzymes. The inhibitors AMPCPR and CID14258187 show more affinity for (a) the 2B06 with score of 5292 and 4888 and (b) for 2AZW with higher docking score of 4902 and 4268. The docking is performed by Patchdock software.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046039&req=5

Figure 5: It shows the distribution of the Nudix inhibitors based on their docking score against the whole structure of the 2B06 and 2AZW Nudix enzymes. The inhibitors AMPCPR and CID14258187 show more affinity for (a) the 2B06 with score of 5292 and 4888 and (b) for 2AZW with higher docking score of 4902 and 4268. The docking is performed by Patchdock software.
Mentions: Docking of 51 inhibitor compounds revealed that the compounds AMPCPR and CID14258187 show more affinity for the 2B06 and 2AZW as compared to other inhibitor compounds. The compound AMPCPR is produced Patchdock score of 5292 and CID14258187 of 4888 in case of 2B06, which is higher than other compounds (Figure 5(a)) (Table 6 see supplementary material) On the other hand for 2AZW, AMPCPR produced score of 4902 and CID14258187 of 4268 (Figure 5(b)). The compounds AMPCPR and CID14258187 bind within the binding site pockets of these Nudix enzymes and surround by RA57, EA62 ,EA58 (2B06) and RA62, EA63, EA66, EA67 (2AZW) binding sites residues (Figure 4). Furthermore, drug likeness properties analyses revealed that the compound CID14258187 shows no violation for the Lipinski rule of 5 (rules for selecting a compound as a potential drug) (Table 4 see supplementary material). On the other hand, the compound AMPCPR is not in agreement of rule of 5 (Table 4 see supplementary material).Therefore, we predict CID14258187 (2R, 3R, 4S, 5R)-2-(6-aminopurin-9-yl)-5-(dichlorophosphoryloxymethyl) oxolane-3, 4-diol) as potential inhibitor of the Nudix enzymes 2B06 and 2AZW.

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus