8DAX

New insights into the P186 flip and oligomeric state of Staphylococcus aureus exfoliative toxin E: implications for the exfoliative mechanism

Summary for 8DAX

• Entry DOI: 10.2210/pdb8dax/pdb
• Descriptor: Exfoliative toxin E (2 entities in total)
• Functional Keywords: ete, toxin
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 57023.82

Authors

Gismene, C.,Nascimento, A.F.Z.,Hernandez-Gonzalez, J.E.,Santisteban, A.R.N.,de Moraes, F.R.,Arni, R.K.,Mariutti, R.B. (deposition date: 2022-06-14, release date: 2022-11-02, Last modification date: 2023-10-18)

Primary citation

Gismene, C.,Hernandez Gonzalez, J.E.,Santisteban, A.R.N.,Ziem Nascimento, A.F.,Dos Santos Cunha, L.,de Moraes, F.R.,de Oliveira, C.L.P.,Oliveira, C.C.,Jocelan Scarin Provazzi, P.,Pascutti, P.G.,Arni, R.K.,Barros Mariutti, R.
Staphylococcus aureus Exfoliative Toxin E, Oligomeric State and Flip of P186: Implications for Its Action Mechanism.
Int J Mol Sci, 23:-, 2022

PubMed Abstract: Staphylococcal 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 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° 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 Å resolution, in which P186(O) adopts two conformations displaying a 180° 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.

PubMed: 36077258
DOI: 10.3390/ijms23179857

Experimental method

X-RAY DIFFRACTION (1.61 Å)