β-Lactoglobulin variants as potential carriers of pramoxine: Comprehensive structural and biophysical studies.
isothermal titration calorimetry
pramoxine
protein engineering
protein-drug interactions
β-Lactoglobulin
Journal
Journal of molecular recognition : JMR
ISSN: 1099-1352
Titre abrégé: J Mol Recognit
Pays: England
ID NLM: 9004580
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
24
07
2023
received:
12
04
2023
accepted:
07
08
2023
medline:
13
9
2023
pubmed:
23
8
2023
entrez:
23
8
2023
Statut:
ppublish
Résumé
β-Lactoglobulin (BLG) is a member of the lipocalin family. As other proteins from this group, BLG can be modified to bind specifically compounds of medical interests. The aim of this study was to evaluate the role of two mutations, L39Y and L58F, in the binding of topical anesthetic pramoxine (PRM) to β-lactoglobulin. Circular dichroism spectroscopy, isothermal titration calorimetry (ITC), and X-ray crystallography were used to understand the mechanisms of BLG-PRM interactions. Studies were performed for three new BLG mutants: L39Y, L58F, and L39Y/L58F. ITC measurements indicated a significant increase in the affinity to the PRM of variants L58F and L39Y. Measurements taken for the double mutant L39Y/L58F showed the additivity of two mutations leading to about 80-fold increase in the affinity to PRM in comparison to natural protein BLG from bovine milk. The determined crystal structures revealed that pramoxine is accommodated in the β-barrel interior of BLG mutants and stabilized by hydrophobic interactions. The observed additive effect of two mutations on drug binding opens the possibility for further designing of new BLG variants with high affinity to selected drugs.
Substances chimiques
pramoxine
068X84E056
Lactoglobulins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3052Informations de copyright
© 2023 John Wiley & Sons Ltd.
Références
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