Crystal Structure of Thermus thermophilus Δ1-Pyrroline-5-carboxylate Dehydrogenase

Eiji Inagaki, Noriyasu Ohshima, Hitomi Takahashi, Chizu Kuroishi, Shigeyuki Yokoyama, Tahir H Tahirov

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Δ1-pyrroline-5-carboxylate dehydrogenase (P5CDh) plays an important role in the metabolic pathway from proline to glutamate. It irreversibly catalyzes the oxidation of glutamate-γ-semialdehyde, the product of the non-enzymatic hydrolysis of Δ1-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 Å 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 Å, 1.9 Å, and 1.4 Å 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.

Original languageEnglish (US)
Pages (from-to)490-501
Number of pages12
JournalJournal of Molecular Biology
Volume362
Issue number3
DOIs
StatePublished - Sep 22 2006

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1-Pyrroline-5-Carboxylate Dehydrogenase
Thermus thermophilus
NAD
Glutamic Acid
Metabolic Networks and Pathways
Proline
Hydrolysis
Ligands
Enzymes
Proteins

Keywords

  • aldehyde dehydrogenase superfamily
  • glutamate-γ-semialdehyde
  • type II hyperprolinemia
  • Δ-pyrroline-5-carboxylate
  • Δ-pyrroline-5-carboxylate dehydrogenase

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Crystal Structure of Thermus thermophilus Δ1-Pyrroline-5-carboxylate Dehydrogenase. / Inagaki, Eiji; Ohshima, Noriyasu; Takahashi, Hitomi; Kuroishi, Chizu; Yokoyama, Shigeyuki; Tahirov, Tahir H.

In: Journal of Molecular Biology, Vol. 362, No. 3, 22.09.2006, p. 490-501.

Research output: Contribution to journalArticle

Inagaki, Eiji ; Ohshima, Noriyasu ; Takahashi, Hitomi ; Kuroishi, Chizu ; Yokoyama, Shigeyuki ; Tahirov, Tahir H. / Crystal Structure of Thermus thermophilus Δ1-Pyrroline-5-carboxylate Dehydrogenase. In: Journal of Molecular Biology. 2006 ; Vol. 362, No. 3. pp. 490-501.
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