8dax

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

spinqualitylabelsall models 8dax, resolution 1.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dax is a 2 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.61Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function L0RUV7_STAAU Publication Abstract from PubMed 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 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 A 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. Staphylococcus aureus Exfoliative Toxin E, Oligomeric State and Flip of P186: Implications for Its Action Mechanism.,Gismene C, Hernandez Gonzalez JE, Santisteban ARN, Ziem Nascimento AF, Dos Santos Cunha L, de Moraes FR, de Oliveira CLP, Oliveira CC, Jocelan Scarin Provazzi P, Pascutti PG, Arni RK, Barros Mariutti R Int J Mol Sci. 2022 Aug 30;23(17). pii: ijms23179857. doi: 10.3390/ijms23179857. PMID:36077258 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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