Faculty Publications
The Response Of Ω-Loop D Dynamics To Truncation Of Trimethyllysine 72 Of Yeast Iso-1-Cytochrome C Depends On The Nature Of Loop Deformation
Document Type
Article
Keywords
Alkaline conformational transition, Apoptosis, Conformationally gated electron transfer, Cooperative substructure dynamics, Cytochrome c
Journal/Book/Conference Title
Journal of Biological Inorganic Chemistry
Volume
20
Issue
5
First Page
805
Last Page
819
Abstract
Trimethyllysine 72 (tmK72) has been suggested to play a role in sterically constraining the heme crevice dynamics of yeast iso-1-cytochrome c mediated by the Ω-loop D cooperative substructure (residues 70-85). A tmK72A mutation causes a gain in peroxidase activity, a function of cytochrome c that is important early in apoptosis. More than one higher energy state is accessible for the Ω-loop D substructure via tier 0 dynamics. Two of these are alkaline conformers mediated by Lys73 and Lys79. In the current work, the effect of the tmK72A mutation on the thermodynamic and kinetic properties of wild-type iso-1-cytochrome c (yWT versus WT∗) and on variants carrying a K73H mutation (yWT/K73H versus WT∗/K73H) is studied. Whereas the tmK72A mutation confers increased peroxidase activity in wild-type yeast iso-1-cytochrome c and increased dynamics for formation of a previously studied His79-heme alkaline conformer, the tmK72A mutation speeds return of the His73-heme alkaline conformer to the native state through destabilization of the His73-heme alkaline conformer relative to the native conformer. These opposing behaviors demonstrate that the response of the dynamics of a protein substructure to mutation depends on the nature of the perturbation to the substructure. For a protein substructure which mediates more than one function of a protein through multiple non-native structures, a mutation could change the partitioning between these functions. The current results suggest that the tier 0 dynamics of Ω-loop D that mediates peroxidase activity has similarities to the tier 0 dynamics required to form the His79-heme alkaline conformer.
Department
Department of Chemistry and Biochemistry
Original Publication Date
7-27-2015
DOI of published version
10.1007/s00775-015-1267-1
Recommended Citation
McClelland, Levi J.; Seagraves, Sean M.; Khan, Md Khurshid Alam; Cherney, Melisa M.; Bandi, Swati; Culbertson, Justin E.; and Bowler, Bruce E., "The Response Of Ω-Loop D Dynamics To Truncation Of Trimethyllysine 72 Of Yeast Iso-1-Cytochrome C Depends On The Nature Of Loop Deformation" (2015). Faculty Publications. 1225.
https://scholarworks.uni.edu/facpub/1225
