dc.contributorUniversidade Estadual Paulista (UNESP)
dc.contributorBrazilian Ctr Res Energy & Mat CNPEM
dc.contributorUniversidade Estadual de Campinas (UNICAMP)
dc.contributorUniversidade de São Paulo (USP)
dc.contributorUniversidade Federal do Rio de Janeiro (UFRJ)
dc.date.accessioned2022-11-30T13:47:54Z
dc.date.accessioned2022-12-20T14:52:05Z
dc.date.available2022-11-30T13:47:54Z
dc.date.available2022-12-20T14:52:05Z
dc.date.created2022-11-30T13:47:54Z
dc.date.issued2022-09-01
dc.identifierInternational Journal Of Molecular Sciences. Basel: Mdpi, v. 23, n. 17, 20 p., 2022.
dc.identifier1422-0067
dc.identifierhttp://hdl.handle.net/11449/237897
dc.identifier10.3390/ijms23179857
dc.identifierWOS:000851108300001
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/5417953
dc.description.abstractStaphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180 degrees flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 angstrom resolution, in which P186(O) adopts two conformations displaying a 180 degrees rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.
dc.languageeng
dc.publisherMdpi
dc.relationInternational Journal Of Molecular Sciences
dc.sourceWeb of Science
dc.subjectStaphylococcal exfoliative toxin E
dc.subjectProline flip
dc.subjectHomodimerization
dc.subjectX-ray diffraction
dc.subjectMolecular dynamics
dc.titleStaphylococcus aureus Exfoliative Toxin E, Oligomeric State and Flip of P186: Implications for Its Action Mechanism
dc.typeArtículos de revistas


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