| http://purl.uniprot.org/citations/24739064 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24739064 | http://www.w3.org/2000/01/rdf-schema#comment | "Glutathione transferases (GSTs) are important enzymes in the metabolism of electrophilic xenobiotic and endobiotic toxic compounds. In addition, human GST A3-3 also catalyzes the double bond isomerization of Δ5-androstene-3,17-dione (Δ(5)-AD) and Δ(5)-pregnene-3,20-dione (Δ(5)-PD), which are the immediate precursors of testosterone and progesterone. In fact, GST A3-3 is the most efficient human enzyme known to exist in the catalysis of these reactions. In this work, we have used density functional theory (DFT) calculations to propose a refined mechanism for the isomerization of Δ(5)-AD catalyzed by GST A3-3. In this mechanism the glutathione (GSH) thiol and Tyr9 catalyze the proton transfer from the Δ(5)-AD C4 atom to the Δ(5)-AD C6 atom, with a rate limiting activation energy of 15.8 kcal · mol(-1). GSH has a dual function, because it is also responsible for stabilizing the negative charge that is formed in the O3 atom of the enolate intermediate. The catalytic role of Tyr9 depends on significant conformational rearrangements of its side chain. Neither of these contributions to catalysis has been observed before. Residues Phe10, Leu111, Ala 208, and Ala 216 complete the list of the important catalytic residues. The mechanism detailed here is based on the GST A3-3:GSH:Δ(4)-AD crystal structure and is consistent with all available experimental data."xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.org/dc/terms/identifier | "doi:10.1021/jp410810q"xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/author | "Ramos M.J."xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/author | "Fernandes P.A."xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/author | "Mannervik B."xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/author | "Dourado D.F."xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/name | "J Phys Chem A"xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/pages | "5790-5800"xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/title | "Isomerization of Delta5-androstene-3,17-dione into Delta4-androstene-3,17-dione catalyzed by human glutathione transferase A3-3: a computational study identifies a dual role for glutathione."xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://purl.uniprot.org/core/volume | "118"xsd:string |
| http://purl.uniprot.org/citations/24739064 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24739064 |
| http://purl.uniprot.org/citations/24739064 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24739064 |
| http://purl.uniprot.org/uniprot/#_Q5JW85-mappedCitation-24739064 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24739064 |
| http://purl.uniprot.org/uniprot/#_Q16772-mappedCitation-24739064 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24739064 |
| http://purl.uniprot.org/uniprot/Q5JW85 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24739064 |
| http://purl.uniprot.org/uniprot/Q16772 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24739064 |