biostudies-literatureUnknown5De Luca AWe provide the first biochemical evidence of a direct interaction between the glutathione transferase P1-1 (GSTP1-1) and the TRAF domain of TNF receptor-associated factor 2 (TRAF2), and describe how ligand binding modulates such an equilibrium. The dissociation constant of the heterocomplex is K(d)=0.3 μM; however the binding affinity strongly decreases when the active site of GSTP1-1 is occupied by the substrate GSH (K(d)≥2.6 μM) or is inactivated by oxidation (Kd=1.7 μM). This indicates that GSTP1-1's TRAF2-binding region involves the GSH-binding site. The GSTP1-1 inhibitor NBDHEX further decreases the complex's binding affinity, as compared with when GSH is the only ligand; this suggests that the hydrophobic portion of the GSTP1-1 active site also contributes to the interaction. We therCell death & diseasee1015https://www.ebi.ac.uk/biostudies/studies/S-EPMC4040697biostudies-literatureThe fine-tuning of TRAF2-GSTP1-1 interaction: effect of ligand binding and in situ detection of the complex.PMC4040697Mei GNicolai EPastore ASerra MFederici LPalumbo CRosato NDe Luca ACaccuri AMfalseThe fine-tuning of TRAF2-GSTP1-1 interaction: effect of ligand binding and in situ detection of the complex.We provide the first biochemical evidence of a direct interaction between the glutathione transferase P1-1 (GSTP1-1) and the TRAF domain of TNF receptor-associated factor 2 (TRAF2), and describe how ligand binding modulates such an equilibrium. The dissociation constant of the heterocomplex is K(d)=0.3 μM; however the binding affinity strongly decreases when the active site of GSTP1-1 is occupied by the substrate GSH (K(d)≥2.6 μM) or is inactivated by oxidation (Kd=1.7 μM). This indicates that GSTP1-1's TRAF2-binding region involves the GSH-binding site. The GSTP1-1 inhibitor NBDHEX further decreases the complex's binding affinity, as compared with when GSH is the only ligand; this suggests that the hydrophobic portion of the GSTP1-1 active site also contributes to the interaction. We ther2014-01-01T00:00:00Z2014 Jan2025-04-04T22:59:00.096Z2019-03-27T01:29:15ZS-EPMC40406972445795910.1038/cddis.2013.529