A disorder to order transition accompanies catalysis in retinaldehyde dehydrogenase type II.
Retinaldehyde dehydrogenase II (RalDH2) converts retinal to the transcriptional regulator retinoic acid in the developing embryo. The x-ray structure of the enzyme revealed an important structural difference between this protein and other aldehyde dehydrogenases of the same enzyme superfamily; a 20-amino acid span in the substrate access channel in retinaldehyde dehydrogenase II is disordered, whereas in other aldehyde dehydrogenases this region forms a well defined wall of the substrate access channel. We asked whether this disordered loop might order during the course of catalysis and provide a means for an enzyme that requires a large substrate access channel to restrict access to the catalytic machinery by smaller compounds that might potentially enter the active site and be metabolized. Our experiments, a combination of kinetic, spectroscopic, and crystallographic techniques, suggest that a disorder to order transition is linked to catalytic activity.
T10 T11 T12 T1 T2 T3 T4 T5 T6 T7 T8 T9
GENE-Y GENE-N GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-N GENE-Y
retinaldehyde dehydrogenase II aldehyde dehydrogenases retinaldehyde dehydrogenase type II Retinaldehyde aldehyde amino acid retinaldehyde aldehyde retinaldehyde Retinaldehyde dehydrogenase II aldehyde dehydrogenases RalDH2