Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase
The effectiveness of β-lactam antibiotics as chemotherapeutic agents to treat bacterial infections is gradually threatened with the emergence of antibiotic resistance mechanism among pathogenic bacteria through the production metallo-β-lactamase (MBL). In this study, we discovered a novel hypothetic...
Saved in:
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Oxford University Press
2017
|
Online Access: | http://psasir.upm.edu.my/id/eprint/61279/1/Danger%20lurking%20in%20the%20unknowns.pdf http://psasir.upm.edu.my/id/eprint/61279/ https://academic.oup.com/jb/article/161/2/167/2725256 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
my.upm.eprints.61279 |
---|---|
record_format |
eprints |
spelling |
my.upm.eprints.612792022-03-04T07:58:10Z http://psasir.upm.edu.my/id/eprint/61279/ Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase Tan, Soo Huei Mohd Yahaya, Normi Leow, Adam Thean Chor Salleh, Abu Bakar Abdul Murad, Abdul Munir Mahadi, Nor Muhammad Abdul Rahman, Mohd Basyaruddin The effectiveness of β-lactam antibiotics as chemotherapeutic agents to treat bacterial infections is gradually threatened with the emergence of antibiotic resistance mechanism among pathogenic bacteria through the production metallo-β-lactamase (MBL). In this study, we discovered a novel hypothetical protein (HP) termed Bleg1_2437 from the genome of alkaliphilic Bacillus lehensis G1 which exhibited MBL-like properties of B3 subclass; but evolutionary divergent from other circulating B3 MBLs. Domain and sequence analysis of HP Bleg1_2437 revealed that it contains highly conserved Zn2+-binding residues such as H54, H56, D58, H59, H131 and H191, important for catalysis, similar with the subclass B3 of MBL. Built 3-D Bleg1_2437 structure exhibited an αββα sandwich layer similar to the well-conserved global topology of MBL superfamily. Other features include a ceiling and floor in the model which are important for accommodation and orientation of β-lactam antibiotics docked to the protein model showed interactions at varying degrees with residues in the binding pocket of Bleg1_2437. Hydrolysis activity towards several β-lactam antibiotics was proven through an in vitro assay using purified recombinant Bleg1_2437 protein. These findings highlight the presence of a clinically important and evolutionary divergent antibiotics-degrading enzyme within the pools of uncharacterized HPs. Oxford University Press 2017 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/61279/1/Danger%20lurking%20in%20the%20unknowns.pdf Tan, Soo Huei and Mohd Yahaya, Normi and Leow, Adam Thean Chor and Salleh, Abu Bakar and Abdul Murad, Abdul Munir and Mahadi, Nor Muhammad and Abdul Rahman, Mohd Basyaruddin (2017) Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase. Journal of Biochemistry, 161 (2). 167 - 186. ISSN 0021-924X; ESSN:1756-2651 https://academic.oup.com/jb/article/161/2/167/2725256 10.1093/jb/mvw058 |
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 |
The effectiveness of β-lactam antibiotics as chemotherapeutic agents to treat bacterial infections is gradually threatened with the emergence of antibiotic resistance mechanism among pathogenic bacteria through the production metallo-β-lactamase (MBL). In this study, we discovered a novel hypothetical protein (HP) termed Bleg1_2437 from the genome of alkaliphilic Bacillus lehensis G1 which exhibited MBL-like properties of B3 subclass; but evolutionary divergent from other circulating B3 MBLs. Domain and sequence analysis of HP Bleg1_2437 revealed that it contains highly conserved Zn2+-binding residues such as H54, H56, D58, H59, H131 and H191, important for catalysis, similar with the subclass B3 of MBL. Built 3-D Bleg1_2437 structure exhibited an αββα sandwich layer similar to the well-conserved global topology of MBL superfamily. Other features include a ceiling and floor in the model which are important for accommodation and orientation of β-lactam antibiotics docked to the protein model showed interactions at varying degrees with residues in the binding pocket of Bleg1_2437. Hydrolysis activity towards several β-lactam antibiotics was proven through an in vitro assay using purified recombinant Bleg1_2437 protein. These findings highlight the presence of a clinically important and evolutionary divergent antibiotics-degrading enzyme within the pools of uncharacterized HPs. |
format |
Article |
author |
Tan, Soo Huei Mohd Yahaya, Normi Leow, Adam Thean Chor Salleh, Abu Bakar Abdul Murad, Abdul Munir Mahadi, Nor Muhammad Abdul Rahman, Mohd Basyaruddin |
spellingShingle |
Tan, Soo Huei Mohd Yahaya, Normi Leow, Adam Thean Chor Salleh, Abu Bakar Abdul Murad, Abdul Munir Mahadi, Nor Muhammad Abdul Rahman, Mohd Basyaruddin Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase |
author_facet |
Tan, Soo Huei Mohd Yahaya, Normi Leow, Adam Thean Chor Salleh, Abu Bakar Abdul Murad, Abdul Munir Mahadi, Nor Muhammad Abdul Rahman, Mohd Basyaruddin |
author_sort |
Tan, Soo Huei |
title |
Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase |
title_short |
Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase |
title_full |
Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase |
title_fullStr |
Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase |
title_full_unstemmed |
Danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein Bleg1_2437 from Bacillus lehensis G1 alkaliphile revealed an evolutionary divergent B3 metallo-beta-lactamase |
title_sort |
danger lurking in the ‘‘unknowns’’: structure-to-function studies of hypothetical protein bleg1_2437 from bacillus lehensis g1 alkaliphile revealed an evolutionary divergent b3 metallo-beta-lactamase |
publisher |
Oxford University Press |
publishDate |
2017 |
url |
http://psasir.upm.edu.my/id/eprint/61279/1/Danger%20lurking%20in%20the%20unknowns.pdf http://psasir.upm.edu.my/id/eprint/61279/ https://academic.oup.com/jb/article/161/2/167/2725256 |
_version_ |
1726793251170549760 |
score |
13.18916 |