Proline dehydrogenase

The tertiary structure of PRODH consists of two interacting protein chains, connected by a mutual interaction between alpha helices of both chains. Each protein chain binds a separate FAD cofactor, necessary for the oxidative activity of the enzyme. The binding of FAD is mediated by electrostatic and non-polar interactions between the cofactor and twelve amino acid residues.[3] In some bacteria, PRODH activity is exhibited in combination with the activity of (S)-1-pyrroline-5-carboxylate dehydrogenase (P5CDH) in an enzyme encoded by Proline Utilization A (putA) gene.[4] Despite being two separate enzymes, eukaryote PRODH and P5CDH also show substrate channeling capabilities.[5]

PRODH catalyzes the first step of proline catabolism, an FAD-dependent oxidation of proline, summarized by a chemical reaction:

L-proline + FAD ${\displaystyle \rightleftharpoons }$ (S)-1-pyrroline-5-carboxylate + FADH₂

PRODH is located in the inner mitochondrial membrane, which enables the electrons to be transferred to ubiquinone, a final electron acceptor of the reaction. The activity of this enzyme regulates endogenous proline content, all the while providing reducing power to the electron transport chain, eventually producing ATP.[6]

PRODH is crucial in regulating intracellular levels of proline, which is an osmotically active compound important in preventing water losses under abiotic stress. Arabidopsis genome contains two PRODH isoforms, PRODH1 and PRODH2, the latter active in response to the osmotic and biotic stress.[7][8] Since the electrons abstracted from L-proline are transferred to electron transport chain, an excessive activity of PRODH may overload the electron transport chain, leading to the generation of reactive oxygen species (ROS), contributing to the hypersensitive response during biotic stress.

As of late 2007, 9 structures have been solved for this class of enzymes, with PDB accession codes 1K87, 1TIW, 1TJ0, 1TJ1, 1TJ2, 1Y56, 2FZM, 2FZN, and 2G37.