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 journalArticlepeer-review

49 Scopus citations


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
Issue number3
StatePublished - Sep 22 2006


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

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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