6ZJC
Crystal structure of Equus ferus caballus glutathione transferase A3-3 in complex with glutathione and triethyltin
Summary for 6ZJC
| Entry DOI | 10.2210/pdb6zjc/pdb |
| Related | 6zj9 |
| Descriptor | Glutathione S-transferase, GLUTATHIONE, Triethyltin bromide, ... (5 entities in total) |
| Functional Keywords | steroid isomerase, detoxication, hormone biosynthesis, organotin compounds, endocrine disrupting chemicals, environmental pollutants, transferase |
| Biological source | Equus caballus (Horse) |
| Total number of polymer chains | 4 |
| Total formula weight | 104300.22 |
| Authors | Skerlova, J.,Ismail, A.,Lindstrom, H.,Sjodin, B.,Mannervik, B.,Stenmark, P. (deposition date: 2020-06-28, release date: 2020-11-18, Last modification date: 2024-01-31) |
| Primary citation | Skerlova, J.,Ismail, A.,Lindstrom, H.,Sjodin, B.,Mannervik, B.,Stenmark, P. Structural and functional analysis of the inhibition of equine glutathione transferase A3-3 by organotin endocrine disrupting pollutants. Environ Pollut, 268:115960-115960, 2021 Cited by PubMed Abstract: Organotin compounds are highly toxic environmental pollutants with neurotoxic and endocrine-disrupting effects. They are potent inhibitors of glutathione transferases (GSTs), thus impeding their detoxication and antioxidant functions. Several GSTs, including equine GST A3-3 (EcaGST A3-3), exhibit steroid double-bond isomerase activity and are involved in the biosynthesis of testosterone and progesterone. We have performed enzyme kinetics analyses of the inhibition of EcaGST A3-3 by organotin compounds. We have also solved crystal structures of EcaGST A3-3 in complexes with glutathione, and with glutathione together with covalently bound triethyltin. Our structural data indicate that the tin atom forms strong bonds with a covalent character not only with the glutathione, but also with a tyrosyl residue of the enzyme itself, thereby preventing the release of the glutathione-organotin adduct and completely blocking the enzyme function. This work presents a structural basis for the general mechanism of GST inhibition by organotin compounds and contributes to the understanding of their neurotoxic and endocrine disrupting effects. PubMed: 33162212DOI: 10.1016/j.envpol.2020.115960 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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