Structural basis of substrate selectivity of Δ(1)-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): semialdehyde chain length.

ABSTRACT: The enzyme Δ(1)-pyrroline-5-carboxylate (P5C) dehydrogenase (aka P5CDH and ALDH4A1) is an aldehyde dehydrogenase that catalyzes the oxidation of γ-glutamate semialdehyde to l-glutamate. The crystal structures of mouse P5CDH complexed with glutarate, succinate, malonate, glyoxylate, and acetate are reported. The structures are used to build a structure-activity relationship that describes the semialdehyde carbon chain length and the position of the aldehyde group in relation to the cysteine nucleophile and oxyanion hole. Efficient 4- and 5-carbon substrates share the common feature of being long enough to span the distance between the anchor loop at the bottom of the active site and the oxyanion hole at the top of the active site. The inactive 2- and 3-carbon semialdehydes bind the anchor l

SUBMITTER: Pemberton TA 

PROVIDER: S-EPMC3915059 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature