Eranthie Weerapana

Promiscuous Metal Site in Hepatitis B Virus X Protein Binds an Fe–S Cluster

Jiahua Chen, Michelle Langton, Patrick Cao, Avital Aaron et autres

Abstract Fe–S clusters are emerging as important cofactors in viral replication but are frequently misassigned as Zn due to their O2-sensitivity and overlapping cysteine-based coordination chemistry. The Hepatitis B virus regulatory protein HBx, which is essential for viral replication and hepatocarcinogenesis, has …

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A nitrite-responsive regulatory RNA locus sustains commensal resilience against nitrosative stress

Ryan T. Fansler, Danile W. Bak, Madison Langford-Butler, Liang Chen et autres

Abstract Commensal microbes in the gastrointestinal tract are central to host health, yet they must adapt to frequent perturbations such as intestinal inflammation that challenges microbial homeostasis. A major challenge during inflammation is exposure to host-derived reactive nitrogen species (RNS), which damage …

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Discovery of a [4Fe-4S] cluster in the PRRSV Nsp1α leader protease reveals host-virus interplay in its downstream functions

Trent Quist, Anastasiya Buzuk, Henry Thanh Nguyen, Kenichiro Takeoka et autres

) is a major global threat to swine production, yet effective antiviral therapies are lacking. The leader protease Nsp1α is essential for viral replication and innate immune suppression, and its N-terminal zinc-finger (ZF) domain is critical for function, although its molecular role …

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Rational engineering of facultative anaerobiosis enables commensal survival in the oxygenated gut

Abigail E. Rose, Madison Langford-Butler, Luisella Spiga, Daniel W. Bak et autres

Abstract Life originated in the absence of oxygen. Despite its substantial energetic advantages, many modern microbes remain obligate anaerobes, confined to anoxic niches such as the mammalian gut. Why these organisms cannot tolerate oxygen has remained unresolved for more than two centuries. …

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Frontiers of redox biology

Takaaki Akaike, Beatriz Álvarez, Ruma Banerjee, Clive Yik‐Sham Chung et autres

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Hydrogen sulfide increases intracellular oxygen and inhibits the HIF response

Joseph Brake, David A. Hanna, Roshan Kumar, Qianni Peng et autres

Oxygen (O 2 ) sensing by hypoxia-inducible factor (HIF) is a principal mechanism by which aerobic organisms adjust cellular energy metabolism and adapt to O 2 limitation. In this study, we show that hydrogen sulfide (H 2 S), a product of host …

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Discovery of a [4Fe-4S] cluster in the PRRSV Nsp1α leader protease reveals host-virus interplay in its downstream functions

Trent Quist, Anastasiya Buzuk, Henry Thanh Nguyen, Ken Takeoka et autres

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV; Betaarterivirus suid ) is a major global threat to swine production, yet effective antiviral therapies are lacking. The leader protease Nsp1α is essential for viral replication and innate immune suppression, and its N-terminal zinc-finger …

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A niche-dependent redox rheostat regulates epithelial stem cell fate

Xi Chen, Krishnan Raghunathan, Bin Bao, Elsy M. Ngwa et autres

Intestinal stem cells (ISCs) reside in regionally variable niches that provide diverse microenvironmental cues such as tissue oxygen status, and morphogen signaling. Integration of these cues with ISC metabolism and fate remains poorly understood. Here, we show that cellular redox balance orchestrates …

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Exploring Metalloproteome Remodeling in Calprotectin-Stressed Acinetobacter baumannii Using Chemoproteomics

Maximillian K. Osterberg, Daniel W. Bak, Claudia Andreini, Minyong Kim et autres

The growth of bacterial pathogens is limited by nutritional immunity, where the infected host deploys transition metal scavenging proteins including calprotectin (CP) to starve the bacterium of essential transition metals. Prior work reveals that CP induces a significant Zn- and Fe-starvation response …

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N ′-(1-Phenylethylidene)benzohydrazide Cytotoxicity Is Lysine-Specific Demethylase 1 Independent and Linked to Iron–Sulfur Cluster Disruption in Ewing Sarcoma

John Sherman, Galen Rask, Bingcong Xiong, E. John Tokarsky et autres

High Resolution Image Download MS PowerPoint Slide The noncompetitive lysine-specific demethylase 1 (LSD1) inhibitors SP-2509 and SP-2577 are N ′-(1-phenylethylidene)benzohydrazides that display potent activity in Ewing sarcoma. They block transcriptional regulation of the causative oncogenic fusion protein EWSR1::FLI1 and cause cell death. …

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Development of a Chemoproteomic Platform to Identify Sites of (Homo)citrullination within Complex Proteomes

Sarah A. Mann, Leonard Barasa, Paul R. Thompson, Eranthie Weerapana

Citrullination and homocitrullination of arginine and lysine can significantly impact protein structure and function. Citrullination of arginine is an enzymatic modification catalyzed by Protein Arginine Deiminases (PADs). Homocitrullination of lysine is a nonenzymatic modification that occurs in the presence of high concentrations …

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Cell-selective multiplexed bioorthogonal noncanonical amino acid tagging for nascent proteomics

Conor Loynd, Soumya Jyoti Singha Roy, Sarah E. Canarelli, Daniel W. Bak et autres

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