Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase
Previously, a hypothetical protein (HP) termed Bleg1_2437 (currently named Bleg1_2478) from Bacillus lehensis G1 was discovered to be an evolutionary divergent B3 subclass metallo-β-lactamase (MBL). Due to the scarcity of clinical inhibitors for B3 MBLs and the divergent nature of Bleg1_2478, this s...
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| Format: | Article |
| Language: | English |
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Multidisciplinary Digital Publishing Institute
2020
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| Online Access: | http://psasir.upm.edu.my/id/eprint/88366/ http://psasir.upm.edu.my/id/eprint/88366/1/ABSTRACT.pdf |
| _version_ | 1848860604674080768 |
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| author | Selvaraju, Gayathri Leow, Adam Thean Chor Salleh, Abu Bakar Mohd Yahaya, Normi |
| author_facet | Selvaraju, Gayathri Leow, Adam Thean Chor Salleh, Abu Bakar Mohd Yahaya, Normi |
| author_sort | Selvaraju, Gayathri |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Previously, a hypothetical protein (HP) termed Bleg1_2437 (currently named Bleg1_2478) from Bacillus lehensis G1 was discovered to be an evolutionary divergent B3 subclass metallo-β-lactamase (MBL). Due to the scarcity of clinical inhibitors for B3 MBLs and the divergent nature of Bleg1_2478, this study aimed to design and characterise peptides as inhibitors against Bleg1_2478. Through in silico docking, RSWPWH and SSWWDR peptides with comparable binding energy to ampicillin were obtained. In vitro assay results showed RSWPWH and SSWWDR inhibited the activity of Bleg1_2478 by 50% at concentrations as low as 0.90 µM and 0.50 µM, respectively. At 10 µM of RSWPWH and 20 µM of SSWWDR, the activity of Bleg1_2478 was almost completely inhibited. Isothermal titration calorimetry (ITC) analyses showed slightly improved binding properties of the peptides compared to ampicillin. Docked peptide-protein complexes revealed that RSWPWH bound near the vicinity of the Bleg1_2478 active site while SSWWDR bound at the center of the active site itself. We postulate that the peptides caused the inhibition of Bleg1_2478 by reducing or blocking the accessibility of its active site from ampicillin, thus hampering its catalytic function. |
| first_indexed | 2025-11-15T12:47:53Z |
| format | Article |
| id | upm-88366 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T12:47:53Z |
| publishDate | 2020 |
| publisher | Multidisciplinary Digital Publishing Institute |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-883662021-12-28T08:46:31Z http://psasir.upm.edu.my/id/eprint/88366/ Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase Selvaraju, Gayathri Leow, Adam Thean Chor Salleh, Abu Bakar Mohd Yahaya, Normi Previously, a hypothetical protein (HP) termed Bleg1_2437 (currently named Bleg1_2478) from Bacillus lehensis G1 was discovered to be an evolutionary divergent B3 subclass metallo-β-lactamase (MBL). Due to the scarcity of clinical inhibitors for B3 MBLs and the divergent nature of Bleg1_2478, this study aimed to design and characterise peptides as inhibitors against Bleg1_2478. Through in silico docking, RSWPWH and SSWWDR peptides with comparable binding energy to ampicillin were obtained. In vitro assay results showed RSWPWH and SSWWDR inhibited the activity of Bleg1_2478 by 50% at concentrations as low as 0.90 µM and 0.50 µM, respectively. At 10 µM of RSWPWH and 20 µM of SSWWDR, the activity of Bleg1_2478 was almost completely inhibited. Isothermal titration calorimetry (ITC) analyses showed slightly improved binding properties of the peptides compared to ampicillin. Docked peptide-protein complexes revealed that RSWPWH bound near the vicinity of the Bleg1_2478 active site while SSWWDR bound at the center of the active site itself. We postulate that the peptides caused the inhibition of Bleg1_2478 by reducing or blocking the accessibility of its active site from ampicillin, thus hampering its catalytic function. Multidisciplinary Digital Publishing Institute 2020 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/88366/1/ABSTRACT.pdf Selvaraju, Gayathri and Leow, Adam Thean Chor and Salleh, Abu Bakar and Mohd Yahaya, Normi (2020) Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase. Molecules, 25 (24). art. no. 5797. pp. 1-19. ISSN 1420-3049 https://www.mdpi.com/1420-3049/25/24/5797 10.3390/molecules25245797 |
| spellingShingle | Selvaraju, Gayathri Leow, Adam Thean Chor Salleh, Abu Bakar Mohd Yahaya, Normi Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase |
| title | Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase |
| title_full | Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase |
| title_fullStr | Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase |
| title_full_unstemmed | Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase |
| title_short | Design and characterisation of inhibitory peptides against Bleg1_2478, an evolutionary divergent B3 metallo-β-lactamase |
| title_sort | design and characterisation of inhibitory peptides against bleg1_2478, an evolutionary divergent b3 metallo-β-lactamase |
| url | http://psasir.upm.edu.my/id/eprint/88366/ http://psasir.upm.edu.my/id/eprint/88366/ http://psasir.upm.edu.my/id/eprint/88366/ http://psasir.upm.edu.my/id/eprint/88366/1/ABSTRACT.pdf |