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PDBsum entry 1s3i

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Hydrolase, oxidoreductase PDB id
1s3i
Jmol
Contents
Protein chain
307 a.a. *
Ligands
BME ×5
Waters ×53
* Residue conservation analysis
PDB id:
1s3i
Name: Hydrolase, oxidoreductase
Title: Crystal structure of the n terminal hydrolase domain of 10- formyltetrahydrofolate dehydrogenase
Structure: 10-formyltetrahydrofolate dehydrogenase. Chain: a. Fragment: nt-fdh,residues 1-310. Synonym: 10-fthfdh, fbp-ci. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: fthfd. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.30Å     R-factor:   0.245     R-free:   0.305
Authors: A.A.Chumanevich,S.A.Krupenko,C.Davies
Key ref:
A.A.Chumanevich et al. (2004). The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase domain. J Biol Chem, 279, 14355-14364. PubMed id: 14729668 DOI: 10.1074/jbc.M313934200
Date:
13-Jan-04     Release date:   27-Jan-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28037  (AL1L1_RAT) -  Cytosolic 10-formyltetrahydrofolate dehydrogenase
Seq:
Struc:
 
Seq:
Struc:
902 a.a.
307 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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)
Bound ligand (Het Group name = BME)
matches with 40.00% similarity
+ 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: 10.1074/jbc.M313934200 J Biol Chem 279:14355-14364 (2004)
PubMed id: 14729668  
 
 
The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase domain.
A.A.Chumanevich, S.A.Krupenko, C.Davies.
 
  ABSTRACT  
 
10-Formyltetrahydrofolate dehydrogenase (FDH) converts 10-formyltetrahydrofolate, a precursor for nucleotide biosynthesis, to tetrahydrofolate. The protein comprises two functional domains: a hydrolase domain that removes a formyl group from 10-formyltetrahydrofolate and a NADP(+)-dependent dehydrogenase domain that reduces the formyl to carbon dioxide. As a first step toward deciphering the catalytic mechanism of the enzyme, we have determined the crystal structure of the hydrolase domain of FDH from rat, solved to 2.3-A resolution. The structure comprises two domains. As expected, domain 1 shares the same Rossmann fold as the related enzymes, methionyl-tRNA-formyltransferase and glycinamide ribonucleotide formyltransferase, but, unexpectedly, the structural similarity between the amino-terminal domain of 10-formyltetrahydrofolate dehydrogenase and methionyl-tRNA-formyltransferase extends to the C terminus of both proteins. The active site contains a molecule of beta-mercaptoethanol that is positioned between His-106 and Asp-142 and that appears to mimic the formate product. We propose a catalytic mechanism for the hydrolase reaction in which Asp-142 polarizes the catalytic water molecule and His-106 orients the carbonyl group of formyl. The structure also provides clues as to how, in the native enzyme, the hydrolase domain transfers its product to the dehydrogenase domain.
 
  Selected figure(s)  
 
Figure 5.
FIG. 5. A stereoview showing the active site residues of N[t]-FDH. A molecule of -mercaptoethanol, situated between Asp-142 and His-106, is shown set against its 2 (F[o] - F[c]) electron density, contoured in blue at 1 . This figure was prepared using PyMOL (W. L. DeLano; available on the World Wide Web at www.pymol.org).
Figure 8.
FIG. 8. Proposed mechanism for the hydrolase reaction of FDH. In this scheme, Asp-142 polarizes a water molecule for hydrolysis of the bond between the carbonyl carbon of formyl and N-10 of THF, and His-106 helps orient the carbonyl group. After catalysis, formate remains bound in the active site until displaced by a molecule of ME.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 14355-14364) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
18712276 Y.Zhang, M.Morar, and S.E.Ealick (2008).
Structural biology of the purine biosynthetic pathway.
  Cell Mol Life Sci, 65, 3699-3724.  
17057331 P.Kursula, H.Schüler, S.Flodin, P.Nilsson-Ehle, D.J.Ogg, P.Savitsky, P.Nordlund, and P.Stenmark (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.
PDB codes: 2bw0 2cfi
16597835 S.N.Reuland, A.P.Vlasov, and S.A.Krupenko (2006).
Modular organization of FDH: Exploring the basis of hydrolase catalysis.
  Protein Sci, 15, 1076-1084.  
15936248 A.Nzila, S.A.Ward, K.Marsh, P.F.Sims, and J.E.Hyde (2005).
Comparative folate metabolism in humans and malaria parasites (part II): activities as yet untargeted or specific to Plasmodium.
  Trends Parasitol, 21, 334-339.  
15807526 P.Z.Gatzeva-Topalova, A.P.May, and M.C.Sousa (2005).
Crystal structure and mechanism of the Escherichia coli ArnA (PmrI) transformylase domain. An enzyme for lipid A modification with 4-amino-4-deoxy-L-arabinose and polymyxin resistance.
  Biochemistry, 44, 5328-5338.
PDB code: 1yrw
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 codes are shown on the right.