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PDBsum entry 2bw0

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protein ligands links
Oxidoreductase PDB id
2bw0
Jmol
Contents
Protein chain
309 a.a. *
Ligands
SO4 ×3
Waters ×469
* Residue conservation analysis
PDB id:
2bw0
Name: Oxidoreductase
Title: Crystal structure of the hydrolase domain of human 10-formyltetrahydrofolate 2 dehydrogenase
Structure: 10-formyltetrahydrofolate dehydrogenase. Chain: a. Fragment: hydrolase domain, residues 1-307. Synonym: 10-fthfdh. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Resolution:
1.7Å     R-factor:   0.172     R-free:   0.200
Authors: D.J.Ogg,P.Stenmark,C.Arrowsmith,A.Edwards,M.Ehn,S.Graslund, M.Hammarstrom,M.Hallberg,T.Kotenyova,P.Nilsson-Ehle, P.Nordlund,C.Persson,J.Sagemark,H.Schuler,M.Sundstrom, A.Thorsell,D.Dobritzsch,J.Weigelt
Key ref:
P.Kursula et al. (2006). Structures of the hydrolase domain of human 10-formyltetrahydrofolate dehydrogenase and its complex with a substrate analogue. Acta Crystallogr D Biol Crystallogr, 62, 1294-1299. PubMed id: 17057331 DOI: 10.1107/S0907444906026849
Date:
07-Jul-05     Release date:   08-Jul-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O75891  (AL1L1_HUMAN) -  Cytosolic 10-formyltetrahydrofolate dehydrogenase
Seq:
Struc:
 
Seq:
Struc:
902 a.a.
309 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     biosynthetic process   1 term 
  Biochemical function     catalytic activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1107/S0907444906026849 Acta Crystallogr D Biol Crystallogr 62:1294-1299 (2006)
PubMed id: 17057331  
 
 
Structures of the hydrolase domain of human 10-formyltetrahydrofolate dehydrogenase and its complex with a substrate analogue.
P.Kursula, H.Schüler, S.Flodin, P.Nilsson-Ehle, D.J.Ogg, P.Savitsky, P.Nordlund, P.Stenmark.
 
  ABSTRACT  
 
10-Formyltetrahydrofolate dehydrogenase is a ubiquitously expressed enzyme in the human body. It catalyses the formation of tetrahydrofolate and carbon dioxide from 10-formyltetrahydrofolate, thereby playing an important role in the human metabolism of one-carbon units. It is a two-domain protein in which the N-terminal domain hydrolyses 10-formyltetrahydrofolate into formate and tetrahydrofolate. The high-resolution crystal structure of the hydrolase domain from human 10-formyltetrahydrofolate dehydrogenase has been determined in the presence and absence of a substrate analogue. The structures reveal conformational changes of two loops upon ligand binding, while key active-site residues appear to be pre-organized for catalysis prior to substrate binding. Two water molecules in the structures mark the positions of key oxygen moieties in the catalytic reaction and reaction geometries are proposed based on the structural data.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 (a) The suggested reaction mechanism for the 10-FTHFD hydrolase step. For clarity, only N10 and the formyl group of the 10-formyl-THF substrate are shown. The water activated by Asp142 attacks the carbon of the formyl group, generating a tetrahedral intermediate stabilized on the one hand by His106 and on the other hand by Asp142. The end products of this reaction are THF and formate. (b) A comparison of the liganded 10-FTHFD (green C atoms) and human GART (pink C atoms) complexed with a substrate analogue, 10-formyl-5,8,10-trideazafolate. His106 and Asp142 are in an identical conformation and two water molecules in the 10-FTHFD complex superimposing with the O atoms of the hydrated formyl group, Wat227 and Wat266, most likely correspond to the positions of the two reactive O atoms during the hydrolase reaction.
 
  The above figure is reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 1294-1299) copyright 2006.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18848533 S.A.Krupenko (2009).
FDH: an aldehyde dehydrogenase fusion enzyme in folate metabolism.
  Chem Biol Interact, 178, 84-93.  
18282486 J.Weigelt, L.D.McBroom-Cerajewski, M.Schapira, Y.Zhao, C.H.Arrowsmith, and C.H.Arrowmsmith (2008).
Structural genomics and drug discovery: all in the family.
  Curr Opin Chem Biol, 12, 32-39.  
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.  
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.