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Spectrum - U.S. Department of Veterans Affairs

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Last Updated: 09 September 2022

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Penicillanic Acid Sulfones Inactivate the Extended-Spectrum β-Lactamase CTX-M-15 through Formation of a Serine-Lysine Cross-Link: an Alternative Mechanism of β-Lactamase Inhibition.

Enmetazobactam and tazobactam are penicillanic acid sulfone inhibitors that differ by an additional methyl group on the triazole ring of enmetazobactam, rendering it zwitterionic. Crystals grown in the presence of enmetazobactam or tazobactam revealed degradation of the Ser70 hydroxyl group and the establishment of a lysinoalanine cross-link between Lys73 and Ser70, two residues critical for catalysis. With CTX-M-15, the Glu166Gln mutant displayed the same cross-link, indicating that this modification is not dependent on Glu166-catalyzed deacylation of the PAS-acylenzyme. The Ser70-Lys73 cross-link configuration shows that epimerization can occur without cross-link development and places the CTX-M-15's Lys73Ala mutation, likely facilitating the creation of the Ser70-Lys73 cross-link. These results support earlier findings that CTX-M-15 deactivation by PAS inhibitors to require protein loss, and they identify a distinct mechanism of u03b2-lactamase inhibition by these agents. IMPORTANCE u03b2-Lactams are the most commonly prescribed antibiotic class for treating bacterial infections, but their continued use is jeopardized by bacteria that produce u03b2-lactamase enzymes that catalyze inactivation. Many bacterial pathogens are resistant to u03b2-lactam resistance in Enterobacteria, with some penicillins and cephalosporins being ineffective, according to the CTX-M family of ESBLs, who are among the key factors to u03b2-lactam resistance in Enterobacterella, which is the primary cause of this disease. PAS exposure caused the formation of a cross-link between Ser70 and Lys73, two residues that are essential to u03b2-lactamase function, according to X-ray crystal structures. This previously undescribed mechanism of inhibition by classical PAS inhibitors improves our knowledge of u03b2-lactamase inhibition by classical PAS inhibitors and supports further, rational inhibitor development.

Source link: https://doi.org/10.1128/mbio.01793-21


Predictors of social functioning and quality of life in schizophrenia and autism spectrum disorder.

Both social cognitive and motor impairments are present in Schizophrenia and Autism Spectrum Disorder. Symptom severity, intelligence, and social awareness have all been suggested predictors of social functioning and quality of life. SZ and ASD discussed challenges in general and cognitive empathy, as well as personal distress, but only SZ demonstrated affective empathy deficits. In both groups, the more negative symptoms the worse QL, and only in ASD, the higher the IQ the higher QL.

Source link: https://doi.org/10.1016/j.psychres.2021.114087

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions