2GER

Crystal Structure and Oxidative Mechanism of Human Pyrroline-5-carboxylate Reductase

Summary for 2GER

• Entry DOI: 10.2210/pdb2ger/pdb
• Descriptor: Pyrroline-5-carboxylate reductase 1 (2 entities in total)
• Functional Keywords: oxidative mechanism of human pyrroline-5-carboxylate, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion: P32322
• Total number of polymer chains: 5
• Total formula weight: 168154.46

Authors

Meng, Z.,Lou, Z.,Liu, Z.,Rao, Z. (deposition date: 2006-03-20, release date: 2006-09-19, Last modification date: 2024-11-20)

Primary citation

Meng, Z.,Lou, Z.,Liu, Z.,Li, M.,Zhao, X.,Bartlam, M.,Rao, Z.
Crystal structure of human pyrroline-5-carboxylate reductase
J.Mol.Biol., 359:1364-1377, 2006

PubMed Abstract: Pyrroline-5-carboxylate reductase (P5CR) is a universal housekeeping enzyme that catalyzes the reduction of Delta(1)-pyrroline-5-carboxylate (P5C) to proline using NAD(P)H as the cofactor. The enzymatic cycle between P5C and proline is very important for the regulation of amino acid metabolism, intracellular redox potential, and apoptosis. Here, we present the 2.8 Angstroms resolution structure of the P5CR apo enzyme, its 3.1 Angstroms resolution ternary complex with NAD(P)H and substrate-analog. The refined structures demonstrate a decameric architecture with five homodimer subunits and ten catalytic sites arranged around a peripheral circular groove. Mutagenesis and kinetic studies reveal the pivotal roles of the dinucleotide-binding Rossmann motif and residue Glu221 in the human enzyme. Human P5CR is thermostable and the crystals were grown at 37 degrees C. The enzyme is implicated in oxidation of the anti-tumor drug thioproline.

PubMed: 16730026
DOI: 10.1016/j.jmb.2006.04.053

Experimental method

X-RAY DIFFRACTION (3.1 Å)