Crystal structure of Thermus thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase.

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Inagaki E, Ohshima N, Takahashi H, Kuroishi C, Yokoyama S, Tahirov TH

Crystal structure of Thermus thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase.

J Mol Biol. 2006 Sep 22;362(3):490-501. Epub 2006 Jul 29.

PubMed ID

16934832 [ View in PubMed

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Abstract

Delta(1)-pyrroline-5-carboxylate dehydrogenase (P5CDh) plays an important role in the metabolic pathway from proline to glutamate. It irreversibly catalyzes the oxidation of glutamate-gamma-semialdehyde, the product of the non-enzymatic hydrolysis of Delta(1)-pyrroline-5-carboxylate, into glutamate with the reduction of NAD(+) into NADH. We have confirmed the P5CDh activity of the Thermus thermophilus protein TT0033 (TtP5CDh), and determined the crystal structure of the enzyme in the ligand-free form at 1.4 A resolution. To investigate the structural basis of TtP5CDh function, the TtP5CDh structures with NAD(+), with NADH, and with its product glutamate were determined at 1.8 A, 1.9 A, and 1.4 A resolution, respectively. The solved structures suggest an overall view of the P5CDh catalytic mechanism and provide insights into the P5CDh deficiencies in the case of the human type II hyperprolinemia.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
NADH	Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial	Protein	Humans	Unknown	Not Available	Details

Polypeptides

Name	UniProt ID
1-pyrroline-5-carboxylate dehydrogenase	P83849	Details