tailieunhanh - Báo cáo khoa học: 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. | ỊFEBS Journal The effect of heme on the conformational stability of micro-myoglobin Hong-Fang Ji1 2 Liang Shen1 2 Rita Grandori3 and Norbert Muller2 1 Shandong ProvincialResearch Center for Bioinformatic Engineering and Technique Center for Advanced Study Shandong University of Technology Zibo China 2 Institute of Organic Chemistry Johannes Kepler University Linz Austria 3 Dipartimento di Biotecnologie e Bioscienze Universita degli Studi di Milano-Bicocca Milan Italy Keywords heme binding micro-myoglobin molecular dynamics simulation protein stability unfolding Correspondence N. Muller Institute of Organic Chemistry Johannes Kepler University 4040 Linz Austria Fax 43 732 2468 8747 Tel 43 732 2468 8746 E-mail Received 28 May 2007 revised 29 October 2007 accepted 5 November 2007 doi Micro-myoglobin the isolated heme-binding subdomain of myoglobin is a valuable model system for the investigation of heme recognition and binding by proteins and provides an example of protein folding induced by cofactor 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 evidence 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 ns in molecular dynamics simulations. Further inspection of the model structures reveals that the role of heme in stabilizing the folded state is not only a result of its direct interactions with binding residues His93 Arg45 and Lys96 but also derives from its shielding 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. The monomeric heme protein myoglobin Mb is found mainly in muscle tissue 1 where its .