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...
Saved in:
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Multidisciplinary Digital Publishing Institute
2020
|
Online Access: | http://psasir.upm.edu.my/id/eprint/88366/1/ABSTRACT.pdf http://psasir.upm.edu.my/id/eprint/88366/ https://www.mdpi.com/1420-3049/25/24/5797 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
my.upm.eprints.88366 |
---|---|
record_format |
eprints |
spelling |
my.upm.eprints.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 |
institution |
Universiti Putra Malaysia |
building |
UPM Library |
collection |
Institutional Repository |
continent |
Asia |
country |
Malaysia |
content_provider |
Universiti Putra Malaysia |
content_source |
UPM Institutional Repository |
url_provider |
http://psasir.upm.edu.my/ |
language |
English |
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. |
format |
Article |
author |
Selvaraju, Gayathri Leow, Adam Thean Chor Salleh, Abu Bakar Mohd Yahaya, Normi |
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 |
author_facet |
Selvaraju, Gayathri Leow, Adam Thean Chor Salleh, Abu Bakar Mohd Yahaya, Normi |
author_sort |
Selvaraju, Gayathri |
title |
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_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_sort |
design and characterisation of inhibitory peptides against bleg1_2478, an evolutionary divergent b3 metallo-β-lactamase |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2020 |
url |
http://psasir.upm.edu.my/id/eprint/88366/1/ABSTRACT.pdf http://psasir.upm.edu.my/id/eprint/88366/ https://www.mdpi.com/1420-3049/25/24/5797 |
_version_ |
1724075502849753088 |
score |
13.160551 |