PDBsum entry 2gdg

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protein Protein-protein interface(s) links
Isomerase PDB id
Protein chains
114 a.a. *
Waters ×465
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Crystal structure of covalently modified macrophage inhibitory factor
Structure: Macrophage migration inhibitory factor. Chain: a, b, c. Synonym: mif, phenylpyruvate tautomerase, glycosylation- inhibiting factor, gif, delayed early response protein 6, der6. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: mif. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
1.45Å     R-factor:   0.148     R-free:   0.183
Authors: P.A.Golubkov,M.L.Hackert
Key ref: P.A.Golubkov et al. (2006). Inactivation of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor by 2-oxo-4-phenyl-3-butynoate. Bioorg Chem, 34, 183-199. PubMed id: 16780921 DOI: 10.1016/j.bioorg.2006.05.001
16-Mar-06     Release date:   04-Jul-06    
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Protein chains
Pfam   ArchSchema ?
P34884  (MIF_MOUSE) -  Macrophage migration inhibitory factor
115 a.a.
114 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.  - Phenylpyruvate tautomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Keto-phenylpyruvate = enol-phenylpyruvate
= enol-phenylpyruvate
   Enzyme class 3: E.C.  - L-dopachrome isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: L-dopachrome = 5,6-dihydroxyindole-2-carboxylate
= 5,6-dihydroxyindole-2-carboxylate
      Cofactor: Zn(2+)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   5 terms 
  Biological process     immune system process   37 terms 
  Biochemical function     chemoattractant activity     7 terms  


DOI no: 10.1016/j.bioorg.2006.05.001 Bioorg Chem 34:183-199 (2006)
PubMed id: 16780921  
Inactivation of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor by 2-oxo-4-phenyl-3-butynoate.
P.A.Golubkov, W.H.Johnson, R.M.Czerwinski, M.D.Person, S.C.Wang, C.P.Whitman, M.L.Hackert.
Macrophage migration inhibitory factor (MIF) is an important immunoregulatory protein that has been implicated in several inflammatory diseases. MIF also has a phenylpyruvate tautomerase (PPT) activity, the role of which remains elusive in these biological activities. The acetylene compound, 2-oxo-4-phenyl-3-butynoate (2-OPB), has been synthesized and tested as a potential irreversible inhibitor of its enzymatic activity. Incubation of the compound with MIF results in the rapid and irreversible loss of the PPT activity. Mass spectral analysis established that the amino-terminal proline, previously implicated as a catalytic base in the PPT-catalyzed reaction, is the site of covalent modification. Inactivation of the PPT activity likely occurs by a Michael addition of Pro-1 to C-4 of the inhibitor. Attempts to crystallize the inactivated complex to confirm the structure of the adduct on the covalently modified Pro-1 by X-ray crystallography were not successful. Nor was it possible to unambiguously interpret electron density observed in the active sites of the native crystals soaked with the inhibitor. This may be due to crystal packing in that the side chain of Glu-16 from an adjacent trimer occupies one active site. However, this crystal contact may be partially responsible for the high-resolution quality of these MIF crystals. Nonetheless, because MIF is a member of the tautomerase superfamily, a group of structurally homologous proteins that share a beta-alpha-beta structural motif and a catalytic Pro-1, 2-OPB may find general use as a probe of tautomerase superfamily members that function as PPTs.