The effect of heme on the conformational stability of micro-myoglobin
Micro-myoglobin, the isolated heme-binding subdomain of myoglobin, is a valuable model system for the investigation of heme recognition and bind-ing by proteins, and provides an example of protein folding induced by co-factor binding. Theoretical studies by molecular dynamics simulations on apo-and holo-micro-myoglobin show that, by contrast with the case of the full-length wild-type protein and in agreement with earlier experimental evi-dence, the apo-protein is not stably folded in a native-like conformation. With the cofactor bound, however, the protein fragment maintains its folded conformation over 1.5 ns in molecular dynamics simulations. Fur-ther inspection of the model structures reveals that the role of heme in sta-bilizing the folded state is not only a result of its direct interactions with binding residues (His93, Arg45 and Lys96), but also derives from its shield-ing effect on a long-range electrostatic interaction between Arg45 and Asp60, which, in the molecular dynamics simulations, apparently triggers the unfolding process of apo-micro-myoglobin.
heme binding micro-myoglobin molecular dynamics simulation protein stability unfolding
Hong-Fang Ji Liang Shen Rita Grandori Norbert M(u)ller
Shandong Provincial Research Center for Bioinformatic Engineering and Technique,Center for Advanc Sh Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Center for Advanc S Dipartimento di Biotecnologie e Bioscienze, Universita degli Studi di Milano-Bicocca, Milan, Italy Institute of Organic Chemistry, Johannes Kepler University, Linz, Austria
国际会议
广州
英文
566-574
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）