Dear all, Registration is now open for the 23rd edition of the Structure Meets Function webinar<https://instruct-eric.eu/tracker/uDdfLt> from Instruct-ERIC. The webinar will take place 13 December 2022 at 12:00 ART (15:00 CET).
This month will feature two excellent speakers, both from IBR-CONICET: Leticia Llarrull and Alejandro Vila. Both speakers participated in Instruct-ERIC's international call for access<https://instruct-eric.eu/tracker/uk8pfu>, which was open for researchers from institutions that hold an MOU with Instruct to access the European facilities. Register Here<https://instruct-eric.eu/tracker/mVQZvp> Moderator: Ana Zeri, LNLS Speaker 1: Leticia Llarrull, IBR-CONICET Talk Title: Advances in structural and functional characterization of the sensor/transducer MecR1 protein of Staphylococcus aureus Abstract: Methicillin resistant Staphylococcus aureus (MRSA) is a pathogen that poses a worldwide threat. Resistance to β-lactams in MRSA is inducible, and MecR1 regulates expression of PBP2a, the main resistance determinant. We are interested in unveiling how the presence of β-lactams activate this metalloprotease, resulting in manifestation of resistance, and on understanding the functional differences with its homologue, BlaR1 from S. aureus, which regulates expression of a serin-β-lactamase. To date, no high-resolution model of full-length MecR1 or BlaR1 is available. Speaker 2: Alejandro Vila, IBR-CONICET Talk Title: In-cell kinetic stability is an essential trait in protein evolution: the case of Metallo-beta-lactamases Abstract: Protein stability is essential for biological function. In contrast to the vast knowledge on the thermodynamics of protein stability in vitro, little is known about the factors governing the in-cell stability, that defines the lifetime of the native state of proteins within the cell. Here we show that the kinetic stability of the metallo-β-lactamase NDM-1 in the bacterial periplasm is optimized to face metal restriction at the host-pathogen interface. NDM-1 is one of the main responsible of providing resistance to carbapenems in pathogenic bacteria. Despite its high stability in vitro, the non-metalated (apo) NDM-1 is unstable in the bacterial periplasm. NMR reveals that metal dissociations endows the apo-enzyme with flexibility at the C-terminal helices, that enable recognition by specific periplasmic proteases, or to aggregation. Zn(II) binding renders the protein refractory to degradation by quenching this flexibility. Apo-NDM-1 is anchored to the outer membrane, a localization that renders it less accessible to the proteases and less prone to aggregate. More recent clinical variants of NDM accumulate mutations that quench this flexibility therefore enhancing their stability towards proteolysis. This work provides direct evidence of how the kinetic stability of a protein optimized within the bacterial cell, and links metallo-β-lactamase-mediated resistance with the cellular metabolism in the periplasm. In cell NMR also reveals information on the degradation pathway, providing insights into the physiology of the bacterial periplasm Reply Forward C ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
