Structure of E6AP in complex with HPV16-E6 and p53 reveals a novel ordered domain important for E3 ligase activation.

High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin transfer reaction, including placement of the E6AP catalytic HECT domain of the ligase concerning the p53 substrate and how E6 itself is protected from ubiquitination. We determined the cryoelectron microscopy (cryo-EM) structure of the E6AP/E6/p53 complex, related the structure to in vivo modeling of the tri-molecular complex, and identified structural interactions associated with activation of the ubiquitin ligase function.

A case of rapidly progressive unilateral non-nephrogenic hemorrhagic bullous calciphylaxis responding to systemic sodium thiosulfate therapy.

Background: Calciphylaxis is a rare and life-threatening condition characterized by cutaneous necrosis resulting from vessel calcification and thrombosis. Commonly associated with end-stage renal disease and hyperparathyroidism, calciphylaxis presents as retiform purpura evolving into necrotic eschars.

Case Report: This report details an atypical case of non-nephrogenic unilateral bullous calciphylaxis in a 71-year-old female, emphasizing the importance of considering calciphylaxis in the differential diagnosis of bullous disorders.

The ester-containing prodrug NT-0796 enhances delivery of the NLRP3 inflammasome inhibitor NDT-19795 to monocytic cells expressing carboxylesterase-1.

NT-0796 is an ester prodrug which is metabolized by carboxylesterase-1 (CES1) to yield the carboxylic acid NDT-19795, an inhibitor of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome. When applied to human monocytes/macrophages which express CES1, however, NT-0796 is much more potent at inhibiting NLRP3 inflammasome activation than is NDT-19795. Comparison of the binding of NDT-19795 and NT-0796 in a cell-based NLRP3 target engagement assay confirms that NDT-19795 is the active species.