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PDBsum entry 2o2r

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
2o2r
Jmol
Contents
Protein chains
498 a.a. *
Ligands
SO4 ×21
NDP ×4
GOL ×4
Waters ×785
* Residue conservation analysis
PDB id:
2o2r
Name: Oxidoreductase
Title: Crystal structure of thE C-terminal domain of rat 10'formyltetrahydrofolate dehydrogenase in complex with nad
Structure: Formyltetrahydrofolate dehydrogenase. Chain: a, b, c, d. Fragment: c-terminal domain, residues 397-902. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: fthfd. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.20Å     R-factor:   0.181     R-free:   0.202
Authors: Y.Tsybovsky,H.Donato,N.I.Krupenko,C.Davies,S.A.Krupenko
Key ref:
Y.Tsybovsky et al. (2007). Crystal structures of the carboxyl terminal domain of rat 10-formyltetrahydrofolate dehydrogenase: implications for the catalytic mechanism of aldehyde dehydrogenases. Biochemistry, 46, 2917-2929. PubMed id: 17302434 DOI: 10.1021/bi0619573
Date:
30-Nov-06     Release date:   06-Mar-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P28037  (AL1L1_RAT) -  Cytosolic 10-formyltetrahydrofolate dehydrogenase
Seq:
Struc:
 
Seq:
Struc:
902 a.a.
498 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.5.1.6  - Formyltetrahydrofolate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Folate Coenzymes
      Reaction: 10-formyltetrahydrofolate + NADP+ + H2O = tetrahydrofolate + CO2 + NADPH
10-formyltetrahydrofolate
+ NADP(+)
+ H(2)O
= tetrahydrofolate
+ CO(2)
+ NADPH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     oxidoreductase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi0619573 Biochemistry 46:2917-2929 (2007)
PubMed id: 17302434  
 
 
Crystal structures of the carboxyl terminal domain of rat 10-formyltetrahydrofolate dehydrogenase: implications for the catalytic mechanism of aldehyde dehydrogenases.
Y.Tsybovsky, H.Donato, N.I.Krupenko, C.Davies, S.A.Krupenko.
 
  ABSTRACT  
 
10-Formyltetrahydrofolate dehydrogenase (FDH) catalyzes an NADP+-dependent dehydrogenase reaction resulting in conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. This reaction is a result of the concerted action of two catalytic domains of FDH, the amino-terminal hydrolase domain and the carboxyl-terminal aldehyde dehydrogenase domain. In addition to participation in the overall FDH mechanism, the C-terminal domain is capable of NADP+-dependent oxidation of short chain aldehydes to their corresponding acids. We have determined the crystal structure of the C-terminal domain of FDH and its complexes with oxidized and reduced forms of NADP. Compared to other members of the ALDH family, FDH demonstrates a new mode of binding of the 2'-phosphate group of NADP via a water-mediated contact with Gln600 that may contribute to the specificity of the enzyme for NADP over NAD. The structures also suggest how Glu673 can act as a general base in both acylation and deacylation steps of the reaction. In the apo structure, the general base Glu673 is positioned optimally for proton abstraction from the sulfur atom of Cys707. Upon binding of NADP+, the side chain of Glu673 is displaced from the active site by the nicotinamide ring and contacts a chain of highly ordered water molecules that may represent a pathway for translocation of the abstracted proton from Glu673 to the solvent. When reduced, the nicotinamide ring of NADP is displaced from the active site, restoring the contact between Cys707 and Glu673 and allowing the latter to activate the hydrolytic water molecule in deacylation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20174634 C.G.Langendorf, T.L.Key, G.Fenalti, W.T.Kan, A.M.Buckle, T.Caradoc-Davies, K.L.Tuck, R.H.Law, and J.C.Whisstock (2010).
The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
  PLoS One, 5, e9280.
PDB code: 3jz4
19933275 K.C.Strickland, L.A.Hoeferlin, N.V.Oleinik, N.I.Krupenko, and S.A.Krupenko (2010).
Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase.
  J Biol Chem, 285, 1627-1633.  
18848533 S.A.Krupenko (2009).
FDH: an aldehyde dehydrogenase fusion enzyme in folate metabolism.
  Chem Biol Interact, 178, 84-93.  
18640390 L.Zhang, G.Perdomo, D.H.Kim, S.Qu, S.Ringquist, M.Trucco, and H.H.Dong (2008).
Proteomic analysis of fructose-induced fatty liver in hamsters.
  Metabolism, 57, 1115-1124.  
18611112 S.A.Marchitti, C.Brocker, D.Stagos, and V.Vasiliou (2008).
Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily.
  Expert Opin Drug Metab Toxicol, 4, 697-720.  
17884809 H.Donato, N.I.Krupenko, Y.Tsybovsky, and S.A.Krupenko (2007).
10-formyltetrahydrofolate dehydrogenase requires a 4'-phosphopantetheine prosthetic group for catalysis.
  J Biol Chem, 282, 34159-34166.  
17655326 T.Wymore, D.W.Deerfield, and J.Hempel (2007).
Mechanistic implications of the cysteine-nicotinamide adduct in aldehyde dehydrogenase based on quantum mechanical/molecular mechanical simulations.
  Biochemistry, 46, 9495-9506.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.