2vcv

Glutathione transferase A3-3 in complex with glutathione and delta-4- androstene-3-17-dione

spinqualitylabelsall models 2vcv, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vcv is a 16 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: ASD, GSH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GSTA3_HUMAN Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Glutathione transferases (GSTs) are abundant enzymes catalyzing the conjugation of hydrophobic toxic substrates with glutathione. In addition to detoxication, human GST A3-3 displays prominent steroid double-bond isomerase activity; e.g. transforming Delta(5)-androstene-3-17-dione into Delta(4)-androstene-3-17-dione (AD). This chemical transformation is a crucial step in the biosynthesis of steroids, such as testosterone and progesterone. In contrast to GST A3-3, the homologous GST A2-2 does not show significant steroid isomerase activity. We have solved the 3D structures of human GSTs A2-2 and A3-3 in complex with AD. In the GST A3-3 crystal structure, AD was bound in an orientation suitable for the glutathione (GSH)-mediated catalysis to occur. In GST A2-2, however, AD was bound in a completely different orientation with its reactive double bond distant from the GSH-binding site. The structures illustrate how a few amino acid substitutions in the active site spectacularly alter the binding mode of the steroid substrate in relation to the conserved catalytic groups and an essentially fixed polypeptide chain conformation. Furthermore, AD did not bind to the GST A2-2-GSH complex. Altogether, these results provide a first-time structural insight into the steroid isomerase activity of any GST and explain the 5000-fold difference in catalytic efficiency between GSTs A2-2 and A3-3. More generally, the structures illustrate how dramatic diversification of functional properties can arise via minimal structural alterations. We suggest a novel structure-based mechanism of the steroid isomerization reaction. Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases.,Tars K, Olin B, Mannervik B J Mol Biol. 2010 Mar 19;397(1):332-40. Epub 2010 Jan 18. PMID:20083122 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutathione S-transferase 3D structures

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