One mechanism of regulating the catalytic activity of protein kinases is through conformational transitions. Despite great diversity in the structural changes involved in the transitions, a certain set of changes within the kinase domain (KD) has been observed for many kinases including Src and CDK2. We investigated this conformational transition computationally to identify the topological features that are energetically critical to the transition. Results from both molecular dynamics sampling and transition path optimization highlight the displacement of the alpha C helix as the major energy barrier, mediating the switch of the KID between the active and down-regulated states. The critical role of the alpha C helix is noteworthy by providing a rationale for a number of activation and deactivation mechanisms known to occur in cells. We find that kinases with the alpha C helix displacement exist throughout the kinome, suggesting that this feature may have emerged early in evolution.