3fyg

From Proteopedia

Revision as of 18:29, 18 December 2007

CRYSTAL STRUCTURE OF TETRADECA-(3-FLUOROTYROSYL)-GLUTATHIONE S-TRANSFERASE

Overview

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.

About this Structure

3FYG is a Single protein structure of sequence from Rattus norvegicus with GPR as ligand. Active as Glutathione transferase, with EC number 2.5.1.18 Known structural/functional Sites: and . Full crystallographic information is available from OCA.

Reference

Conformational changes in the crystal structure of rat glutathione transferase M1-1 with global substitution of 3-fluorotyrosine for tyrosine., Xiao G, Parsons JF, Tesh K, Armstrong RN, Gilliland GL, J Mol Biol. 1998 Aug 14;281(2):323-39. PMID:9698551

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