Methotrexate binding causes structural and functional changes in lung cystatin

• Authors: Mohd Shahnawaz Khan , Medha Priyadarshini , Sadia Sumbul , Bilqees Bano
• Languages of publication: EN

Abstracts

EN

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.

Keywords

EN

FTIR; goat lung cystatin; methotrexate; emphysema

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2010
• Volume: 57
• Issue: 4
• Pages: 499-503

Dates

published

2010

received

2009-09-20

revised

2010-05-14

accepted

2010-11-03

(unknown)

2010-11-29

Contributors

author

Mohd Shahnawaz Khan

• Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, U.P., India

author

Medha Priyadarshini

• Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, U.P., India

author

Sadia Sumbul

• Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, U.P., India

author

Bilqees Bano

• Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, U.P., India

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