Structural studies of metal-free metallothionein.
We report the first molecular dynamics calculations on the structure of metal-free betaalpha recombinant human metallothionein, with comparison to the two isolated fragments, alpha-rhMT and beta-rhMT, starting from a linear synthesized strand as well as a demetallated conformation. Following a 5000 ps MM3/MD calculation, the cysteine side chains were found to populate the outside surface of the metal-free protein, regardless of the initial conformation. The polypeptide backbone adopted a random coil conformation when starting from the linear strand, however, it retained a significant amount of secondary structure when starting from the demetallated conformation. We propose that the inverted cysteinyl sulfur orientation facilitates the binding of the metal ions to form the proteolytically stable, metallated protein.
Rigby
Kelly E
KE
Department of Chemistry, University of Western Ontario, London, Ont., Canada N6A 5B7. Martin.Stillman@uwo.ca
Stillman
Martin J
MJ
D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D008668:Metallothionein / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D013696:Temperature
D008670:Metals; D021122:Protein Subunits; D008668:Metallothionein