PDBsum entry 2bja

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Oxidoreductase PDB id
Protein chains
516 a.a. *
NAD ×2
ACT ×2
_CL ×2
Waters ×808
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal analysis of 1-pyrroline-5-carboxylate dehydrogenase from thermus with bound nadh
Structure: 1-pyrroline-5-carboxylate dehydrogenase. Chain: a, b. Engineered: yes. Other_details: oxidation of cys to cso (s-hydroxyl -cysteine) at a 322 and b 322
Source: Thermus thermophilus. Organism_taxid: 300852. Strain: hb8. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Hexamer (from PDB file)
1.9Å     R-factor:   0.176     R-free:   0.212
Authors: E.Inagaki,T.H.Tahirov
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
01-Feb-05     Release date:   09-Mar-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q5SI02  (Q5SI02_THET8) -  1-pyrroline-5-carboxylate dehydrogenase
516 a.a.
516 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   3 terms 
  Biochemical function     nucleotide binding     5 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.
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 [].
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 [].
  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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21168532 F.He, and P.J.DiMario (2011).
Drosophila delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDh) is required for proline breakdown and mitochondrial integrity-Establishing a fly model for human type II hyperprolinemia.
  Mitochondrion, 11, 397-404.  
20133651 D.Srivastava, J.P.Schuermann, T.A.White, N.Krishnan, N.Sanyal, G.L.Hura, A.Tan, M.T.Henzl, D.F.Becker, and J.J.Tanner (2010).
Crystal structure of the bifunctional proline utilization A flavoenzyme from Bradyrhizobium japonicum.
  Proc Natl Acad Sci U S A, 107, 2878-2883.
PDB code: 3haz
20936198 R.Orth, T.Böttcher, and S.A.Sieber (2010).
The biological targets of acivicin inspired 3-chloro- and 3-bromodihydroisoxazole scaffolds.
  Chem Commun (Camb), 46, 8475-8477.  
18369526 J.J.Tanner (2008).
Structural biology of proline catabolism.
  Amino Acids, 35, 719-730.  
  18931443 J.P.Schuermann, T.A.White, D.Srivastava, D.B.Karr, and J.J.Tanner (2008).
Three crystal forms of the bifunctional enzyme proline utilization A (PutA) from Bradyrhizobium japonicum.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 949-953.  
  17554163 E.Inagaki, N.Ohshima, K.Sakamoto, N.D.Babayeva, H.Kato, S.Yokoyama, and T.H.Tahirov (2007).
New insights into the binding mode of coenzymes: structure of Thermus thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase complexed with NADP+.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 462-465.
PDB code: 2ehq
17344208 T.A.White, N.Krishnan, D.F.Becker, and J.J.Tanner (2007).
Structure and kinetics of monofunctional proline dehydrogenase from Thermus thermophilus.
  J Biol Chem, 282, 14316-14327.
PDB code: 2g37
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