3FYG
CRYSTAL STRUCTURE OF TETRADECA-(3-FLUOROTYROSYL)-GLUTATHIONE S-TRANSFERASE
Summary for 3FYG
| Entry DOI | 10.2210/pdb3fyg/pdb |
| Descriptor | MU CLASS TETRADECA-(3-FLUOROTYROSYL)-GLUTATHIONE S-TRANSFERASE OF ISOENZYME, (9R,10R)-9-(S-GLUTATHIONYL)-10-HYDROXY-9,10-DIHYDROPHENANTHRENE (3 entities in total) |
| Functional Keywords | transferase, 3-fluorotyrosine, unnatural amino acid, three-dimensional structure, detoxification enzyme |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cytoplasm: P04905 |
| Total number of polymer chains | 2 |
| Total formula weight | 53108.42 |
| Authors | Xiao, G.,Parsons, J.F.,Armstrong, R.N.,Gilliland, G.L. (deposition date: 1997-08-07, release date: 1999-06-01, Last modification date: 2024-11-06) |
| Primary citation | Xiao, G.,Parsons, J.F.,Tesh, K.,Armstrong, R.N.,Gilliland, G.L. Conformational changes in the crystal structure of rat glutathione transferase M1-1 with global substitution of 3-fluorotyrosine for tyrosine. J.Mol.Biol., 281:323-339, 1998 Cited by PubMed Abstract: The structure of the tetradeca-(3-fluorotyrosyl) M1-1 GSH transferase (3-FTyr GSH transferase), a protein in which tyrosine residues are globally substituted by 3-fluorotyrosines has been determined at 2.2 A resolution. This variant was produced to study the effect on the enzymatic mechanism and the structure was undertaken to assess how the presence of the 3-fluorotyrosyl residue influences the protein conformation and hence its function. Although fluorinated amino acid residues have frequently been used in biochemical and NMR investigations of proteins, no structure of a protein that has been globally substituted with a fluorinated amino acid has previously been reported. Thus, this structure represents the first crystal structure of such a protein containing a library of 14 (28 crystallographically distinct) microenvironments from which the nature of the interactions of fluorine atoms with the rest of the protein can be evaluated. Numerous conformational changes are observed in the protein structure as a result of substitution of 3-fluorotyrosine for tyrosine. The results of the comparison of the crystal structure of the fluorinated protein with the native enzyme reveal that conformational changes are observed for most of the 3-fluorotyrosines. The largest differences are seen for residues where the fluorine, the OH, or both are directly involved in interactions with other regions of the protein or with a symmetry-related molecule. The fluorine atoms of the 3-fluorotyrosine interact primarily through hydrogen bonds with other residues and water molecules. In several cases, the conformation of a 3-fluorotyrosine is different in one of the monomers of the enzyme from that observed in the other, including different hydrogen-bonding patterns. Altered conformations can be related to differences in the crystal packing interactions of the two monomers in the asymmetric unit. The fluorine atom on the active-site Tyr6 is located near the S atom of the thioether product (9R,10R)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene and creates a different pattern of interactions between 3-fluorotyrosine 6 and the S atom. Studies of these interactions help explain why 3-FTyr GSH transferase exhibits spectral and kinetic properties distinct from the native GSH transferase. PubMed: 9698551DOI: 10.1006/jmbi.1998.1935 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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