PDBsum entry: 2iy6

Oxidoreductase

PDB id: 2iy6

Contents

Protein chains

516 a.a. *

Ligands

FLC ×2

MPD ×8

MRD ×5

Metals

_CL ×2

_NA ×2

Waters ×1157

* Residue conservation analysis

PDB id:

2iy6

Name:

Oxidoreductase

Title:

1-pyrroline-5-carboxylate dehydrogenase from thermus with bound citrate

Structure:

1-pyrroline-5-carboxylate dehydrogenase. Chain: a, b. Engineered: yes

Source:

Thermus thermophilus. Organism_taxid: 300852. Strain: hb8. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Biol. unit:

Hexamer (from PDB file)

Resolution:

1.8Å R-factor: 0.140 R-free: 0.170

Authors:

E.Inagaki,K.Sakamoto,M.Nishio,S.Yokoyama

Key ref:

E.Inagaki et al. (2006). Crystal structure of Thermus thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase. J Mol Biol, 362, 490-501. PubMed id: 16934832 DOI: 10.1016/j.jmb.2006.07.048

Date:

13-Jul-06 Release date: 24-Jul-06

Protein chains

Q5SI02  (Q5SI02_THET8) -  1-pyrroline-5-carboxylate dehydrogenase

Seq: 516 a.a.

Struc: 516 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: metabolic process (3 terms)
• Biochemical function: nucleotide binding (4 terms)

DOI no: 10.1016/j.jmb.2006.07.048

J Mol Biol 362:490-501 (2006)

PubMed id: 16934832

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

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

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.

Selected figure(s)

Figure 5.
Figure 5. The binding modes of NAD^+ and NADH. (a) and (b) F[o]–F[c] omit map of bound coenzymes and disordered residues in the coenzyme-binding site. The difference Fourier electron density is contoured at 3σ. (a) F[o]–F[c] omit map of the bound NAD^+, the S atom of Cys322 and the residues Thr289−Gly291 in TtP5CDh-NAD. Atoms corresponding to the minor conformer are colored white. The hydrogen bond between the Thr289 O atom and NAD^+ is drawn by a dotted line. (b) F[o]–F[c] omit map of the bound NADH, the S and O^δ atoms of oxydated Cys322 (S-hydroxy-cysteine) and the residues Thr289−Gly291 in TtP5CDh-NADH. The disordered pyrophosphate group of NADH and an alternative model of the S and O^δ atoms of S-hydroxy-cysteine are colored white. (c) and (d) Views of the catalytic site in TtP5CDh–NAD corresponding to the major conformer of NAD^+ (c), and in TtP5CDh–NADH (d). One of the alternative conformers of oxidized Cys322 is colored white. All the panels were prepared using PyMol [http://www.pymol.org].

Figure 9.
Figure 9. Mutation leading to HPII. (a) A view of water-mediated hydrogen bond network around Ser326 in the TtP5CDh ternary complex model. The S326L is shown as a stick model in white. (b) A view of around Gly486 in the TtP5CDh ternary complex model. The backbones of residues 1−485 of chain A and B are colored green and blue, respectively. The backbones of the residues 486−516 of chain A and B are colored white and light pink, respectively. The Glu288 and Cys322 are shown by sticks. All the panels were prepared with PyMol [http://www.pymol.org].

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 362, 490-501) copyright 2006.

Figures were selected by an automated process.