Functional and conformational changes in the aspartic protease cardosin A induced by TFE.
Conformational and functional changes of cardosin A, an aspartic protease of vegetal origin, in the presence of 2,2,2-trifluoroethanol (TFE), were assessed. TFE induced alterations of cardosin activity and conformation that differed with the solvent concentration. MD simulations showed that there are significant local alterations in protein flexibility and TFE molecules were found to replace several hydration molecules in the active site of the enzyme. This may explain some of the activity loss observed in the presence of TFE, especially at low TFE concentrations, as well as the recovery of enzyme activity upon aqueous dilution, indicating the release of the TFE molecules from the active site.
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
Ana Sofia
AS
Fraga
Ana Cristina
AC
Esteves
Nuno
N
Micaelo
Pedro F
PF
Cruz
Rui M M
RM
Brito
Margaret
M
Nutley
Alan
A
Cooper
Marlene M T
MM
Barros
Euclides M V
EM
Pires
D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain / Q000187:drug effects; D003198:Computer Simulation; D004789:Enzyme Activation / Q000187:drug effects; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D014270:Trifluoroethanol / Q000494:pharmacology*
D010940:Plant Proteins; D014270:Trifluoroethanol; D016282:Aspartic Acid Endopeptidases; C097455:aspartic proteinases, Cynara cardunculus