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

Soo Huei Tan, Yahaya M. Normi, Adam Thean Chor Leow, Abu Bakar Salleh, Abdul Munir Abd. Murad, Nor Muhammad Mahadi, Mohd Basyaruddin Abdul Rahman

Research output: Contribution to journalArticle

Abstract

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 aαbβbβaα 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 b-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 blactam 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.

Original languageEnglish
Pages (from-to)167-186
Number of pages20
JournalJournal of Biochemistry
Volume161
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

Fingerprint

Bacilli
beta-Lactamases
Bacillus
Anti-Bacterial Agents
Lactams
Proteins
Protein Sequence Analysis
Microbial Drug Resistance
Catalysis
Bacterial Infections
Ceilings
Hydrolysis
Genome
Assays
Bacteria
Genes
Topology
Enzymes

Keywords

  • Antibiotic resistance
  • Bacillus lehensis G1
  • Beta-lactam antibiotics
  • Hypothetical protein
  • Metallobeta- lactamase.

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry
  • Molecular Biology

Cite this

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; Normi, Yahaya M.; Leow, Adam Thean Chor; Salleh, Abu Bakar; Abd. Murad, Abdul Munir; Mahadi, Nor Muhammad; Rahman, Mohd Basyaruddin Abdul.

In: Journal of Biochemistry, Vol. 161, No. 2, 01.02.2017, p. 167-186.

Research output: Contribution to journalArticle

Tan, Soo Huei ; Normi, Yahaya M. ; Leow, Adam Thean Chor ; Salleh, Abu Bakar ; Abd. Murad, Abdul Munir ; Mahadi, Nor Muhammad ; Rahman, Mohd Basyaruddin Abdul. / 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. In: Journal of Biochemistry. 2017 ; Vol. 161, No. 2. pp. 167-186.
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