2gsr
|
STRUCTURE OF PORCINE CLASS PI GLUTATHIONE S-TRANSFERASE
OverviewOverview
The crystal structure of class Pi glutathione S-transferase from porcine, lung (pGST P1-1) in complex with glutathione sulphonate has been refined, at 2.11 A resolution, to a crystallographic R-factor of 16.5% for 21, 165, unique reflections. The refined structure includes 3314 protein atoms, 46, inhibitor (glutathione sulphonate) atoms and 254 water molecules. The, model shows good stereochemistry, with root-mean-square deviations from, ideal bond lengths and bond angles of 0.011 A and 2.8 degrees, respectively. The estimated root-mean-square co-ordinate error is 0.2 A., The protein is a dimer assembled from identical subunits of 207 amino acid, residues. The tertiary structure of the pGST P1 subunit is organized as, two domains, the N-terminal domain (domain I, residues 1 to 74) and the, larger C-terminal domain (domain II, residues 81 to 207). Glutathione, sulphonate, a competitive inhibitor, binds to the G-site region (i.e. the, glutathione-binding region) of the active site located on each subunit., Each G-site is, however, structurally dependent of the neighbouring, subunit as structural elements forming a fully functional G-site are, provided by both subunits, with domain I as the major supporting, framework. A number of direct and water-mediated polar interactions are, involved in sequestering the glutathione analogue at the G-site. The, extended conformation assumed by the enzyme-bound inhibitor as well as the, strategic interactions between inhibitor and protein, closely resemble, those observed for the physiological substrate, reduced glutathione bound, at the active site of class Mu glutathione S-transferase 3-3. Hydrogen, bonding between the sulphonyl moiety of the inhibitor and the hydroxyl, group of an evolutionary conserved tyrosine residue, Tyr7, provides the, first direct structural evidence for a catalytic protein group in, glutathione S-transferases that is involved in the activation of the, substrate glutathione. The catalytic role for Tyr7 has subsequently been, confirmed by mutagenesis and kinetic studies. Comparison of the known, crystal structures for class Pi, class Mu and class Alpha isoenzymes, indicates that the cytosolic glutathione S-transferases share a common, fold and that the structural features for catalysis are similar.
About this StructureAbout this Structure
2GSR is a Single protein structure of sequence from Sus scrofa. This structure superseeds the now removed PDB entry 1GSR. Active as Glutathione transferase, with EC number 2.5.1.18 Full crystallographic information is available from OCA.
ReferenceReference
Refined crystal structure of porcine class Pi glutathione S-transferase (pGST P1-1) at 2.1 A resolution., Dirr H, Reinemer P, Huber R, J Mol Biol. 1994 Oct 14;243(1):72-92. PMID:7932743
Page seeded by OCA on Wed Nov 21 11:22:08 2007