%0 Journal Article
%A Liptak, Matthew D.
%A Fagerlund, Robert D.
%A Ledgerwood, Elizabeth C.
%A Wilbanks, Sigurd M.
%A Bren, Kara L.
%D 2011
%T The Proapoptotic G41S Mutation to Human Cytochrome c Alters the Heme Electronic Structure and Increases the Electron Self-Exchange Rate
%U https://acs.figshare.com/articles/journal_contribution/The_Proapoptotic_G41S_Mutation_to_Human_Cytochrome_i_c_i_Alters_the_Heme_Electronic_Structure_and_Increases_the_Electron_Self_Exchange_Rate/2693011
%R 10.1021/ja106328k.s001
%2 https://acs.figshare.com/ndownloader/files/4368955
%K Proapoptotic G 41S Mutation
%K Human Cytochrome c Alters
%K Heme Electronic Structure
%K ring C
%K DFT
%K pyrrole ring C
%K G 41S mutation
%K G 41S Hs cyt c
%K heme pyrrole ring
%K NMR
%K WT
%X The naturally occurring G41S mutation to human (Hs) cytochrome (cyt) c enhances apoptotic activity based upon previous in vitro and in vivo studies, but the molecular mechanism underlying this enhancement remains unknown. Here, X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and density functional theory (DFT) calculations have been used to identify the structural and electronic differences between wild-type (WT) and G41S Hs cyt c. S41 is part of the hydrogen bonding network for propionate 7 of heme pyrrole ring A in the X-ray structure of G41S Hs cyt c and, compared to WT, G41S Hs cyt c has increased spin density on pyrrole ring C and a faster electron self-exchange rate. DFT calculations illustrate an electronic mechanism where structural changes near ring A can result in electronic changes at ring C. Since ring C is part of the solvent-exposed protein surface, we propose that this heme electronic structure change may ultimately be responsible for the enhanced proapoptotic activity of G41S Hs cyt c.
%I ACS Publications