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| Title: | Leishmania donovani trypanothione reductase: Role of urea and guanidine hydrochloride in modulation of functional and structural properties |
| Authors: | Rai, Smita
Dwivedi, UN
Goyal, Neena |
| Keywords: | Leishmania donovani
trypanothione reductase
Unfolding
Intermediate
CD
Fluorescence
Molten globule |
| Issue Date: | 2009 |
| Citation: | Biochimica et Biophysica Acta-1794-2009-1474 |
| Abstract: | Trypanothione reductase [TR], an NADPH-dependent disulfide oxidoreductase, unique to kinetoplastid parasites including Trypanosoma and Leishmania, is a validated target for the design of improved drugs. TR is a stable homodimer with a FAD molecule tightly bound to each subunit. In this paper, structure, function, stability properties and cofactor protein interactions of recombinant TR from Leishmania donovani were investigated under equilibrium unfolding/denaturing conditions. Urea induced unfolding was non-reductive in nature and led to the formation of partially folded intermediate. This intermediate species lacks catalytic activity and characteristic conformation of native LdTR but has significant secondary structure and could be partially reactivated. Guanidine hydrochloride-induced irreversible denaturation was marked by the presence of molten globule intermediate. Reactivation and cross-linking experiments clearly demonstrated that the loss of activity at lower denaturant concentrations was not coincided by dimer dissociation or structural unfolding. The studies demonstrate that functional conformation and stability is largely governed by ionic interactions and active centre site disulphide plays a vital role in helping to maintaining functional conformation. The results obtained from this study provide intriguing insight into the possible mechanism/s of modulation of structure, function and stability of LdTR induced by the cationic, guanidine hydrochloride and the neutral denaturant, urea. |
| URI: | http://hdl.handle.net/123456789/564 |
| Appears in Collections: | Biochemistry
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| goyalneena-7342-Biochimica et Biophysica Acta-1794- 2009-1474.pdf | | 680Kb | Adobe PDF | View/Open |
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