TY - JOUR
T1 - Crystal Structure of Thermus thermophilus Δ1-Pyrroline-5-carboxylate Dehydrogenase
AU - Inagaki, Eiji
AU - Ohshima, Noriyasu
AU - Takahashi, Hitomi
AU - Kuroishi, Chizu
AU - Yokoyama, Shigeyuki
AU - Tahirov, Tahir H.
PY - 2006/9/22
Y1 - 2006/9/22
N2 - 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.
AB - 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.
KW - aldehyde dehydrogenase superfamily
KW - glutamate-γ-semialdehyde
KW - type II hyperprolinemia
KW - Δ-pyrroline-5-carboxylate
KW - Δ-pyrroline-5-carboxylate dehydrogenase
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U2 - 10.1016/j.jmb.2006.07.048
DO - 10.1016/j.jmb.2006.07.048
M3 - Article
C2 - 16934832
AN - SCOPUS:33748094644
VL - 362
SP - 490
EP - 501
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 3
ER -