Structural dynamics of PMP-D2: An experimental and theoretical study

PMP-D2 is a 35 residue polypeptide cross-linked by three disulfide bridges. Its three-dimensional structure has been previously determined (Mer et al. Biochemistry 1994, 33, 15397-15407). Further investigation of its structure identified a crucial interaction between W25 and K10 and a double salt bridge between the positively charged K10 and the negatively charged E2 and D13. Chemical shift calculations reveal some discrepancies with experimental data concerning the structure. Heteronuclear relaxation studies, which observed broadening of K10 side chain proton resonances, and molecular dynamics simulations subsequently suggest that these discrepancies are due to slow conformational exchange in the molecule. The heteronuclear relaxation studies and visual inspection of the three-dimensional structure suggest that the residues which exhibit slow exchange form a network and move in a concerted manner.