The impact of structural biology on neurobiology

摘要

Canavan disease is a fatal neu-rodegenerative disorder whose symptoms, including loss of motor skills and muscle control, appear in early infancy and typically progress very rapidly, with death usually occurring within the first decade of life. Unlike the case with many neurological disorders where the underlying genetic defects remain to be elucidated, Canavan disease is caused by defects in a single gene, the acy2 gene that encodes for the enzyme aspartoacylase. Recent biochemical studies have begun to characterize the mechanistic properties (1) and structural properties (2) of aspartoacylase, but progress in our understanding of this disease has been slowed by the absence of high-resolution structures of this critical metabolic enzyme. This gap has now been filled by the determination of the structures of both the rat and human forms of aspartoacylase reported by Bitto et al. (3) in this issue of PNAS.