Structural Characterization and Transcriptional Regulation of Cypin: the Role in Neuronal Dendrite Branching

This work focuses on the identification of specific structural properties of cypin that lead to the multifunctional roles in guanine metabolism and dendrite development. We first employed phylogenetic analysis and computational structure modeling techniques to construct a three dimensional structural model of cypin. In addition, we used a combination of protein structure analysis, experimental kinetic studies, and cell culture tests to uncover novel potential ligands for cypin. We obtained a list of compounds that demonstrate higher binding affinity to GDA than does guanine. Our results provide evidence that an in silico drug discovery strategy coupled with in vitro verification can be successfully implemented to discover compounds that may have therapeutic value for the treatment of diseases and disorders where GDA activity is abnormal. The discovery of intrinsic regulators of cypin expression aids in our understanding of molecular mechanisms underlying dendritic patterning, and hence, synaptic plasticity, learning and memory.