| Autor: |
Karnchanapandh K; Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, Thailand., Hanpaibool C; Center of Excellence in Biocatalyst and Sustainable Biotechnology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand., Sanachai K; Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand., Rungrotmongkol T; Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, Thailand.; Center of Excellence in Biocatalyst and Sustainable Biotechnology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Feb-Mar; Vol. 42 (4), pp. 1617-1628. Date of Electronic Publication: 2023 Apr 26. |
| DOI: |
10.1080/07391102.2023.2201360 |
| Abstrakt: |
C. difficile or Clostridioides difficile infection (CDI) is currently one of the major causes of epidemics worldwide. Toxin B from Clostridioides difficile toxin B (TcdB) infection is the main target protein inhibiting CDI recurrence. Clinical research suggested that bezlotoxumab's (Bez) efficiency is significantly reduced in neutralizing the B2 strain compared to the B1 strain. The monoclonal antibody (mAb) functions by binding to the epitope 1 and 2 regions in the combined repetitive oligopeptide (CROP) domain. Some binding residues are distinctively different between B1 and B2 strains. In this work, we aimed to elucidate and compare insights into the interaction of toxins B1 and B2 in complex with Bez by using all-atom molecular dynamics (MD) simulations and binding free energy calculations. The predicted Δ G binding values suggested that the antibody (Ab) could bind to toxin B1 significantly better than B2, supported by higher salt bridge and hydrogen bonding (H-bonding) interactions, as well as the number of contact residues between the two focused proteins. The toxin B1 residues important for binding with Bez were E1878, T1901, E1902, F1905, N1941, V1946, N2031, T2032, E2033, V2076, V2077, and E2092. The lower susceptibility of Bez towards toxin B2 was primarily due to a change of residue E2033 from glutamate to alanine (A2033) and the loss of E1878 and E1902 contributions, as determined by the intermolecular interaction changes from the dynamic residue interaction network (dRIN) analysis. The obtained data strengthen our understanding of Bez/toxin B binding. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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