Post-translational phosphorylation and its associated conformational changes regulate a wide range of subcellular processes. Pin1 is central to many of these cell signaling pathways in normal and aberrant subcellular processes, catalyzing the cis�trans isomerization of proline in phosphorylated serine/threonine-proline motifs in many proteins. The effects of phosphorylation on Pin1 substrates and the basis for Pin1 recognition and catalysis are not well understood. We present the conformational consequences of phosphorylation on Pin1 substrate analogues and the mechanism by which the catalytic domain selects its substrates: conformational selection. Furthermore, dynamical correlated motions present in apoPin1 are present in Pin1 of the enzyme�substrate complex when the substrate is in the transition state configuration, suggesting that these motions play significant roles during catalytic turnover. These results elucidate the mechanism of Pin1 recognition and further our understanding of the of post-translational phosphorylation and cis�trans isomerization.

Conformational selection in the recognition of phosphorylated substrates by the catalytic domain of Human Pin1

243rd National Meeting (2012)

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