Abstract
Aberrant folding of important proteins caused by genetic mutations is closely correlated to many diseases. Due to the important physiological role in excitable cells, the activity and level of creatine kinase (CK) play a crucial role in maintaining body functions. Muscle CK deficiency disease was identified by an unusual CK activity decrease in an acute myocardial infarction patient caused by the single point mutation D54G. In this research, it was found that the D54G mutant had substantially decreased activity, substrate binding affinity and stability. Spectroscopic experiments indicated that the mutation impaired the structure of CK, which resulted in a partially unfolded state with more hydrophobic exposure and exposed Trp residues. The inability to fold to the functional compact state made the mutant be prone to aggregate upon microenvironmental stresses, and might gradually decrease the CK level of the patient.
Original language | English (US) |
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Pages (from-to) | 392-401 |
Number of pages | 10 |
Journal | International Journal of Biochemistry and Cell Biology |
Volume | 39 |
Issue number | 2 |
DOIs | |
State | Published - 2007 |
Keywords
- Aggregation
- Creatine kinase
- Creatine kinase deficiency disease
- Folding intermediate
- Misfolding
- Structural stability
ASJC Scopus subject areas
- Biochemistry
- Cell Biology