caa a22 4500 605507767 CHVBK 20210128100633.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00775-015-1267-1 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1267-1 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 [Elektronische Daten] [Levi McClelland, Sean Seagraves, Md. Khan, Melisa Cherney, Swati Bandi, Justin Culbertson, Bruce Bowler] 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. SBIC, 2015 Cooperative substructure dynamics nationallicence Cytochrome c nationallicence Alkaline conformational transition nationallicence Conformationally gated electron transfer nationallicence Apoptosis nationallicence ET : Electron transfer nationallicence gated ET : Conformationally gated electron transfer nationallicence GdnHCl : Guanidine hydrochloride nationallicence iso-1-Cyt c : Iso-1-cytochrome c nationallicence tmK : Trimethyllysine nationallicence McClelland Levi Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut Seagraves Sean Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut Khan Md Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut Cherney Melisa Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut Bandi Swati Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut Culbertson Justin Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut Bowler Bruce Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 805-819 0949-8257 20:5<805 2015 20 775 https://doi.org/10.1007/s00775-015-1267-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1267-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- McClelland Levi Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut NATIONALLICENCE 700 1- Seagraves Sean Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut NATIONALLICENCE 700 1- Khan Md Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut NATIONALLICENCE 700 1- Cherney Melisa Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut NATIONALLICENCE 700 1- Bandi Swati Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut NATIONALLICENCE 700 1- Culbertson Justin Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut NATIONALLICENCE 700 1- Bowler Bruce Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Dynamics, University of Montana, 59812, Missoula, MT, USA aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 805-819 0949-8257 20:5<805 2015 20 775