Abstract
Molecular dynamics study on dynamical structures of mutant cardiac troponin T, which have been reported to be involved in serious cardiac diseases, were carried out. Calculations were done on troponin T fragment (residue 204 to 230) using Software Amber ver.7 based on a crystal structure of human troponin CIT complex in Protein Data Bank (1J1E). Iteration was done in TIP3 water sphere (25 angstrom of diameter) with 0.002 ps time step in non periodic condition at constant temperature (310 K). A mutant troponinT which lacks K210 (ΔK210) is one of the causes of familial dilated cardiomyopathy (DCM) and skinned fiber in which this mutation was introduced has been reported to have reduced calcium sensitivity (Morimoto et al. 2002). According to the analysis by chou fasman protein secondary structure prediction, we made a ΔK210 mutant model of troponin T fragment to keep forming alfa helix by shift and the rotation (1/3.6 turn) of the residues in N terminal side connected to the deleted one. We found that the dynamical structure of this mutant model showed two characteristics compared with that of wild type, that is; 1) an alfa helix formed by residue 204 to 223 shrank by about quarter turn as a direct result of deletion, and 2) acidic side chain of G204 and basic side chain of K208 exhibited strong electrostatic interaction. These changes observed in this model may modify the mobility and orientation of N terminus of troponin T (TnT1) and C terminus of troponin T (TnT2), which are thought to be essential for regulation of muscle contraction. [Jpn J Physiol 54 Suppl:S121 (2004)]
