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Dead-end complex, l...
Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation
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- Kuang, Qie (author)
- KTH,Strukturell bioteknik,Department of Biosciences and Nutrition, Karolinska Institutet
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- Purhonen, Pasi (author)
- Karolinska Institutet,KTH,Strukturell bioteknik,Department of Biosciences and Nutrition, Karolinska Institutet
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- Alander, Johan (author)
- Karolinska Institutet
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- Svensson, Richard (author)
- Karolinska Institutet
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- Hoogland, Veronika (author)
- Karolinska Institutet
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- Winerdal, Jens (author)
- Karolinska Institutet
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- Spahiu, Linda (author)
- Karolinska institutet
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- Ottosson-Wadlund, Astrid (author)
- Karolinska Insitutet
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- Jegerschöld, Caroline (author)
- Karolinska Institutet,KTH,Skolan för kemi, bioteknologi och hälsa (CBH),Department of Biosciences and Nutrition, Karolinska Institutet
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- Morgenstern, Ralf (author)
- Karolinska Institutet
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- Hebert, Hans (author)
- KTH,Strukturell bioteknik,Department of Biosciences and Nutrition, Karolinska Institutet
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(creator_code:org_t)
- 2017-08-11
- 2017
- English.
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
- Related links:
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https://doi.org/10.1...
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Abstract
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- Microsomal glutathione transferase 1 (MGST1) is a detoxification enzyme belonging to the Membrane Associated Proteins in Eicosanoid and Glutathione Metabolism (MAPEG) superfamily. Here we have used electron crystallography of two-dimensional crystals in order to determine an atomic model of rat MGST1 in a lipid environment. The model comprises 123 of the 155 amino acid residues, two structured phospholipid molecules, two aliphatic chains and one glutathione (GSH) molecule. The functional unit is a homotrimer centered on the crystallographic three-fold axes of the unit cell. The GSH substrate binds in an extended conformation at the interface between two subunits of the trimer supported by new in vitro mutagenesis data. Mutation of Arginine 130 to alanine resulted in complete loss of activity consistent with a role for Arginine 130 in stabilizing the strongly nucleophilic GSH thiolate required for catalysis. Based on the new model and an electron diffraction data set from crystals soaked with trinitrobenzene, that forms a dead-end Meisenheimer complex with GSH, a difference map was calculated. The map reveals side chain movements opening a cavity that defines the second substrate site.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Medicinsk bioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Medical Biotechnology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Kuang, Qie
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Purhonen, Pasi
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Alander, Johan
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Svensson, Richar ...
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Hoogland, Veroni ...
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Winerdal, Jens
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Spahiu, Linda
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Ottosson-Wadlund ...
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Jegerschöld, Car ...
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Morgenstern, Ral ...
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Hebert, Hans
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- About the subject
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Industrial Biote ...
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and Medical Biotechn ...
- Articles in the publication
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Scientific Repor ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet