4LGZ

Structure of mouse 1-Pyrroline-5-Carboxylate Dehydrogenase (ALDH4A1) complexed with acetate

Summary for 4LGZ

• Entry DOI: 10.2210/pdb4lgz/pdb
• Related: 3V9G 3V9H 3V9I 3V9J 3V9K 3V9L 4LH1 4LH2 4LH3 4hl0
• Descriptor: Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial, ACETIC ACID, PENTAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: proline catabolism, substrate recognition, rossmann fold, oxidoreductase
• Biological source: Mus musculus (mouse)
• Cellular location: Mitochondrion matrix : Q8CHT0
• Total number of polymer chains: 2
• Total formula weight: 124625.19

Authors

Pemberton, T.A.,Tanner, J.J. (deposition date: 2013-06-30, release date: 2013-08-28, Last modification date: 2024-02-28)

Primary citation

Pemberton, T.A.,Tanner, J.J.
Structural basis of substrate selectivity of Delta (1)-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): Semialdehyde chain length.
Arch.Biochem.Biophys., 538:34-40, 2013

PubMed 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 loop but are too short to reach the oxyanion hole. Inhibition of P5CDH by glyoxylate, malonate, succinate, glutarate, and l-glutamate is also examined. The Ki values are 0.27 mM for glyoxylate, 58 mM for succinate, 30 mM for glutarate, and 12 mM for l-glutamate. Curiously, malonate is not an inhibitor. The trends in Ki likely reflect a trade-off between the penalty for desolvating the carboxylates of the free inhibitor and the number of compensating hydrogen bonds formed in the enzyme-inhibitor complex.

PubMed: 23928095
DOI: 10.1016/j.abb.2013.07.024

Experimental method

X-RAY DIFFRACTION (1.675 Å)