- Tytuł:
- Methotrexate binding causes structural and functional changes in lung cystatin
- Autorzy:
-
Khan, Mohd
Priyadarshini, Medha
Sumbul, Sadia
Bano, Bilqees - Powiązania:
- https://bibliotekanauki.pl/articles/1040310.pdf
- Data publikacji:
- 2010
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
FTIR
goat lung cystatin
methotrexate
emphysema - Opis:
- Regulation of cysteine proteinases and their inhibitors is of utmost importance in diseases like lung cancer, chronic inflammatory conditions such as asthma, emphysema, and idiopathic pulmonary fibrosis. Protease-antiprotease imbalance accelerates disease progression. In the present study, the effect of antineoplastic and antirheumatic drug methotrexate (MTX) on lung cystatin (a cysteine protease inhibitor) was studied to explore drug induced changes in functional and structural integrity of the protein. The basic binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of MTX with goat lung cystatin (GLC-I). Stern-Volmer analysis of MTX-GLC-I system at different temperatures indicates the presence of static component in the quenching mechanism. The thermodynamic parameters ΔH0 and ΔS0 were -3.8 kJ/mol and 94.97 J•mol-1•K-1, respectively, indicating that both hydrogen bonds and hydrophobic interactions played a major role in the binding of MTX to GLC-I. Methotrexate (7 µM) caused complete inactivation of lung cystatin after 6 hours. The results of FT-IR spectroscopy reflect perturbation of the goat lung cystatin on interaction with MTX. Methotrexate induced loss of function change in the inhibitor could provide a rationale for the off target tissue injury caused by the drug and for the design of agents against such an injury.
- Źródło:
-
Acta Biochimica Polonica; 2010, 57, 4; 499-503
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł