{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T06:40:22Z","timestamp":1759992022386},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,1,15]]},"abstract":"<jats:p>The dimeric structure of certain cytosolic GSTs (glutathione S-transferases) is stabilized by a hydrophobic lock-and-key motif at their subunit interface. In hGSTA1-1 (human class Alpha GST with two type-1 subunits), the key consists of two residues, Met51 and Phe52, that fit into a hydrophobic cavity (lock) in the adjacent subunit. SEC (size-exclusion chromatography)\u2013HPLC, far-UV CD and tryptophan fluorescence of the M51A and M51A\/F52S mutants indicated the non-disruptive nature of these mutations on the global structure. While the M51A mutant retained 80% of wild-type activity, the activity of the M51A\/F52S was markedly diminished, indicating the importance of Phe52 in maintaining the correct conformation at the active site. The M51A and M51A\/F52S mutations altered the binding of ANS (8-anilinonaphthalene-l-sulphonic acid) at the H-site by destabilizing helix 9 in the C-terminal region. Data from urea unfolding studies show that the dimer is destabilized by both mutations and that the dimer dissociates to aggregation-prone monomers at low urea concentrations before global unfolding. Although not essential for the assembly of the dimeric structure of hGSTA1-1, both Met51 and Phe52 in the intersubunit lock-and-key motif play important structural roles in maintaining the catalytic and ligandin functions and stability of the GST dimer.<\/jats:p>","DOI":"10.1042\/bj20051066","type":"journal-article","created":{"date-parts":[[2006,3,2]],"date-time":"2006-03-02T09:20:39Z","timestamp":1141291239000},"page":"523-528","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The intersubunit lock-and-key motif in human glutathione transferase A1-1: role of the key residues Met51 and Phe52 in function and dimer stability"],"prefix":"10.1042","volume":"393","author":[{"given":"Carla\u00a0S.","family":"Alves","sequence":"first","affiliation":[{"name":"Protein Structure\u2013Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa"}]},{"given":"Diane\u00a0C.","family":"Kuhnert","sequence":"additional","affiliation":[{"name":"Protein Structure\u2013Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa"}]},{"given":"Yasien","family":"Sayed","sequence":"additional","affiliation":[{"name":"Protein Structure\u2013Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa"}]},{"given":"Heini\u00a0W.","family":"Dirr","sequence":"additional","affiliation":[{"name":"Protein Structure\u2013Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa"}]}],"member":"288","published-online":{"date-parts":[[2005,12,23]]},"reference":[{"key":"2021112217162135800_B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3600001","article-title":"Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily","volume":"360","author":"Sheehan","year":"2001","journal-title":"Biochem. 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