In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase
Background: The emergence of multidrug-resistant strains of Staphylococcus aureus, there is an urgent need for the development of new antimicrobials which are narrow and pathogen specific. Aim: In this context, the present study is aimed to have a control on the staphylococcal infections by targetin...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2014-01-01
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| Series: | Journal of Pharmacy and Bioallied Sciences |
| Subjects: | |
| Online Access: | http://www.jpbsonline.org/article.asp?issn=0975-7406;year=2014;volume=6;issue=3;spage=158;epage=166;aulast=Kumar |
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| author | Pasupuleti Santhosh Kumar Yellapu Nanda Kumar Uppu Venkateswara Prasad Sthanikam Yeswanth Vimjam Swarupa Gopal Sowjenya Katari Venkatesh Lokanathan Srikanth Valasani Koteswara Rao Potukuchi Venkata Gurunatha Krishna Sarma |
| author_facet | Pasupuleti Santhosh Kumar Yellapu Nanda Kumar Uppu Venkateswara Prasad Sthanikam Yeswanth Vimjam Swarupa Gopal Sowjenya Katari Venkatesh Lokanathan Srikanth Valasani Koteswara Rao Potukuchi Venkata Gurunatha Krishna Sarma |
| author_sort | Pasupuleti Santhosh Kumar |
| collection | DOAJ |
| description | Background: The emergence of multidrug-resistant strains of Staphylococcus aureus, there is an urgent need for the development of new antimicrobials which are narrow and pathogen specific. Aim: In this context, the present study is aimed to have a control on the staphylococcal infections by targeting the unique and essential enzyme; porphobilinogen synthase (PBGS) catalyzes the condensation of two molecules of δ-aminolevulinic acid, an essential step in the tetrapyrrole biosynthesis. Hence developing therapeutics targeting PBGS will be the promising choice to control and manage the staphylococcal infections. 4,5-dioxovalerate (DV) is known to inhibit PBGS. Materials and Methods: In view of this, in this study, novel dioxovalerate derivatives (DVDs) molecules were designed so as to inhibit PBGS, a potential target of S. aureus and their inhibitory activity was predicted using molecular docking studies by molecular operating environment. The 3D model of PBGS was constructed using Chlorobium vibrioform (Protein Data Bank 1W1Z) as a template by homology modeling method. Results: The built structure was close to the crystal structure with Z score − 8.97. Molecular docking of DVDs into the S. aureus PBGS active site revealed that they are showing strong interaction forming H-bonds with the active sites of K248 and R217. The ligand-receptor complex of DVD13 showed a best docking score of − 14.4555 kcal/mol among DV and all its analogs while the substrate showed docking score of − 13.0392 kcal/mol showing interactions with S199, K217 indicating that DVD13 can influence structural variations on the enzyme and thereby inhibiting the enzyme. Conclusion: The substrate analog DVD13 is showing significant interactions with active site of PBGS and it may be used as a potent inhibitor to control S. aureus infections. |
| first_indexed | 2024-12-14T09:53:22Z |
| format | Article |
| id | doaj.art-77f1b591d1524cad87cd77316584c51c |
| institution | Directory Open Access Journal |
| issn | 0975-7406 0976-4879 |
| language | English |
| last_indexed | 2024-12-14T09:53:22Z |
| publishDate | 2014-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Pharmacy and Bioallied Sciences |
| spelling | doaj.art-77f1b591d1524cad87cd77316584c51c2022-12-21T23:07:28ZengWolters Kluwer Medknow PublicationsJournal of Pharmacy and Bioallied Sciences0975-74060976-48792014-01-016315816610.4103/0975-7406.135246In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthasePasupuleti Santhosh KumarYellapu Nanda KumarUppu Venkateswara PrasadSthanikam YeswanthVimjam SwarupaGopal SowjenyaKatari VenkateshLokanathan SrikanthValasani Koteswara RaoPotukuchi Venkata Gurunatha Krishna SarmaBackground: The emergence of multidrug-resistant strains of Staphylococcus aureus, there is an urgent need for the development of new antimicrobials which are narrow and pathogen specific. Aim: In this context, the present study is aimed to have a control on the staphylococcal infections by targeting the unique and essential enzyme; porphobilinogen synthase (PBGS) catalyzes the condensation of two molecules of δ-aminolevulinic acid, an essential step in the tetrapyrrole biosynthesis. Hence developing therapeutics targeting PBGS will be the promising choice to control and manage the staphylococcal infections. 4,5-dioxovalerate (DV) is known to inhibit PBGS. Materials and Methods: In view of this, in this study, novel dioxovalerate derivatives (DVDs) molecules were designed so as to inhibit PBGS, a potential target of S. aureus and their inhibitory activity was predicted using molecular docking studies by molecular operating environment. The 3D model of PBGS was constructed using Chlorobium vibrioform (Protein Data Bank 1W1Z) as a template by homology modeling method. Results: The built structure was close to the crystal structure with Z score − 8.97. Molecular docking of DVDs into the S. aureus PBGS active site revealed that they are showing strong interaction forming H-bonds with the active sites of K248 and R217. The ligand-receptor complex of DVD13 showed a best docking score of − 14.4555 kcal/mol among DV and all its analogs while the substrate showed docking score of − 13.0392 kcal/mol showing interactions with S199, K217 indicating that DVD13 can influence structural variations on the enzyme and thereby inhibiting the enzyme. Conclusion: The substrate analog DVD13 is showing significant interactions with active site of PBGS and it may be used as a potent inhibitor to control S. aureus infections.http://www.jpbsonline.org/article.asp?issn=0975-7406;year=2014;volume=6;issue=3;spage=158;epage=166;aulast=KumarDioxovoleratehomology modelingmolecular operating environmentporphobilinogen synthase |
| spellingShingle | Pasupuleti Santhosh Kumar Yellapu Nanda Kumar Uppu Venkateswara Prasad Sthanikam Yeswanth Vimjam Swarupa Gopal Sowjenya Katari Venkatesh Lokanathan Srikanth Valasani Koteswara Rao Potukuchi Venkata Gurunatha Krishna Sarma In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase Journal of Pharmacy and Bioallied Sciences Dioxovolerate homology modeling molecular operating environment porphobilinogen synthase |
| title | In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase |
| title_full | In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase |
| title_fullStr | In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase |
| title_full_unstemmed | In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase |
| title_short | In silico designing and molecular docking of a potent analog against Staphylococcus aureus porphobilinogen synthase |
| title_sort | in silico designing and molecular docking of a potent analog against staphylococcus aureus porphobilinogen synthase |
| topic | Dioxovolerate homology modeling molecular operating environment porphobilinogen synthase |
| url | http://www.jpbsonline.org/article.asp?issn=0975-7406;year=2014;volume=6;issue=3;spage=158;epage=166;aulast=Kumar |
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