Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbes
Abstract Background Many of the pathogenic microbes use trehalose–6–phosphate phosphatase (TPP) enzymes for biosynthesis of sugar trehalose from trehalose–6–phosphate (T6P) in their pathway of infection and proliferation. Therefore, the present work is an approach to design new generation candidate...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-02-01
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| Series: | Beni-Suef University Journal of Basic and Applied Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43088-019-0028-6 |
| _version_ | 1818387772268871680 |
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| author | H. R. Umesh K. V. Ramesh K. S. Devaraju |
| author_facet | H. R. Umesh K. V. Ramesh K. S. Devaraju |
| author_sort | H. R. Umesh |
| collection | DOAJ |
| description | Abstract Background Many of the pathogenic microbes use trehalose–6–phosphate phosphatase (TPP) enzymes for biosynthesis of sugar trehalose from trehalose–6–phosphate (T6P) in their pathway of infection and proliferation. Therefore, the present work is an approach to design new generation candidate drugs to inhibit TPP through in silico methods. Results Blast P and Clustal Omega phylogenetic analysis of TPP sequences were done for 12 organisms that indicate and confirm the presence of three conserved active site regions of known TPPs. Docking studies of 3D model of TPP with 17 phytochemicals revealed most of them have good binding affinity to an enzyme with rutin exhibiting highest affinity (Binding energy of − 7 kcal/mole). It has been found that during docking, phytochemical leads bind to active site region 3 of TPP sequences which coordinates Mg2+ and essential for catalysis. Conclusions Binding poses and distance measurement of TPP-phytochemical complexes of rutin, carpaine, stigmasterol, β-caryophyllene, and α-eudesmol reveals that the lead phytochemicals were in close proximity with most of the active site amino acids of region 3 (distance range from 1.796 to 2.747 Ao). This confirms the tight binding between enzyme and leads which may pave way for the discovery of new generation drugs against TPP producing pathogenic microbes to manage diseases. |
| first_indexed | 2024-12-14T04:15:15Z |
| format | Article |
| id | doaj.art-5da164e1f3684324bceb6c1d3afe85de |
| institution | Directory Open Access Journal |
| issn | 2314-8543 |
| language | English |
| last_indexed | 2024-12-14T04:15:15Z |
| publishDate | 2020-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Beni-Suef University Journal of Basic and Applied Sciences |
| spelling | doaj.art-5da164e1f3684324bceb6c1d3afe85de2022-12-21T23:17:32ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85432020-02-019111410.1186/s43088-019-0028-6Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbesH. R. Umesh0K. V. Ramesh1K. S. Devaraju2Research and Development Centre, Bharathiar UniversityPost graduate Department of Biochemistry, Dayananda Sagar College of BiosciencesDepartment of Biochemistry, Karnatak UniversityAbstract Background Many of the pathogenic microbes use trehalose–6–phosphate phosphatase (TPP) enzymes for biosynthesis of sugar trehalose from trehalose–6–phosphate (T6P) in their pathway of infection and proliferation. Therefore, the present work is an approach to design new generation candidate drugs to inhibit TPP through in silico methods. Results Blast P and Clustal Omega phylogenetic analysis of TPP sequences were done for 12 organisms that indicate and confirm the presence of three conserved active site regions of known TPPs. Docking studies of 3D model of TPP with 17 phytochemicals revealed most of them have good binding affinity to an enzyme with rutin exhibiting highest affinity (Binding energy of − 7 kcal/mole). It has been found that during docking, phytochemical leads bind to active site region 3 of TPP sequences which coordinates Mg2+ and essential for catalysis. Conclusions Binding poses and distance measurement of TPP-phytochemical complexes of rutin, carpaine, stigmasterol, β-caryophyllene, and α-eudesmol reveals that the lead phytochemicals were in close proximity with most of the active site amino acids of region 3 (distance range from 1.796 to 2.747 Ao). This confirms the tight binding between enzyme and leads which may pave way for the discovery of new generation drugs against TPP producing pathogenic microbes to manage diseases.https://doi.org/10.1186/s43088-019-0028-6Trehalose–6–phosphate phosphataseBinding affinityIn silicoPhytochemicalRutin |
| spellingShingle | H. R. Umesh K. V. Ramesh K. S. Devaraju Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbes Beni-Suef University Journal of Basic and Applied Sciences Trehalose–6–phosphate phosphatase Binding affinity In silico Phytochemical Rutin |
| title | Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbes |
| title_full | Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbes |
| title_fullStr | Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbes |
| title_full_unstemmed | Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbes |
| title_short | Molecular docking studies of phytochemicals against trehalose–6–phosphate phosphatases of pathogenic microbes |
| title_sort | molecular docking studies of phytochemicals against trehalose 6 phosphate phosphatases of pathogenic microbes |
| topic | Trehalose–6–phosphate phosphatase Binding affinity In silico Phytochemical Rutin |
| url | https://doi.org/10.1186/s43088-019-0028-6 |
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