Figure 3.

Alterations in the three-dimensional fold of Epo are caused by charge repulsion. Mutation of residues shown in red to Glu causes conformational changes because it leads to charge repulsion between the Glu78 mutant and Asp96, and repulsion between the Glu94 and Glu/Asp97 mutants and Glu18 or Glu21. Ala substitution at position 78 or 97 results in slight structural changes, suggesting that the substantial alterations in protein conformation observed upon introduction of Glu in these regions are not solely due to charge repulsion, but may also be caused by the elimination of stabilizing interactions such as a hydrogen bond or salt bridge. PDB file 1BUY was used to generate this figure.