A small molecule chemical chaperone optimizes its unfolded state contraction and denaturant like properties
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
A small molecule chemical chaperone optimizes its unfolded state contraction and denaturant like properties
|
|
| Creator |
Sharma, Sunny
Sarkar, Suparna Paul, Simanta Sarani Roy, Syamal Chattopadhyay, Krishnananda Chattopadhyay1 |
|
| Subject |
Infectious Diseases and Immunology
Structural Biology & Bioinformatics |
|
| Description |
Protein aggregation is believed to occur through the formation of misfolded conformations. It is expected
that, in order to minimize aggregation, an effective small molecule chaperone would destabilize these
intermediates. To study the mechanism of a chemical chaperone, we have designed a series of mutant
proteins in which a tryptophan residue experiences different local environments and solvent exposures. We
show that these mutants correspond to a series of conformationally altered proteins with varying degree of
misfolding stress and aggregation propensities. Using arginine as a model small molecule, we show that a
combination of unfolded state contraction and denaturant like properties results in selective targeting and
destabilization of the partially folded proteins. In comparison, the effect of arginine towards the folded like
control mutant, which is not aggregation prone, is significantly less. Other small molecules, lacking either of
the above two properties, do not offer any specificity towards the misfolded proteins.
|
|
| Date |
2013
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/2262/1/SCIENTIFIC_REPORTS__V_._3_____Article_Number_3525;2013[1].pdf
Sharma, Sunny and Sarkar, Suparna and Paul, Simanta Sarani and Roy, Syamal and Chattopadhyay, Krishnananda Chattopadhyay1 (2013) A small molecule chemical chaperone optimizes its unfolded state contraction and denaturant like properties. Scientific Reports, 3 (3525). |
|
| Relation |
http://dx.doi.org/10.1038/srep03525
http://www.eprints.iicb.res.in/2262/ |
|