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Structural and func...
Structural and functional analysis of the inhibition of equine glutathione transferase A3-3 by organotin endocrine disrupting pollutants
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- Škerlová, Jana (författare)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Ismail, Aram (författare)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Lindström, Helena (författare)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Sjödin, Birgitta (författare)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Mannervik, Bengt (författare)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Stenmark, Pål (författare)
- Stockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Strukturell biokemi,Forskargrupper vid Lunds universitet,Structural Biochemistry,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- Engelska.
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 268
- Relaterad länk:
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https://doi.org/10.1...
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https://doi.org/10.1...
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Organotin compounds are highly toxic environmental pollutants with neurotoxic and endocrinedisrupting 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.
Ämnesord
- NATURVETENSKAP -- Geovetenskap och miljövetenskap (hsv//swe)
- NATURAL SCIENCES -- Earth and Related Environmental Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Organometallic compounds
- Endocrine disrupting chemicals
- Steroid isomerization
- Detoxication
- Hormone biosynthesis
- Structural biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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