Publications by authors named "Joseph D Hurley"

Article Synopsis
  • G-protein-coupled receptors (GPCRs) play a crucial role in regulating human physiology and are common targets for drugs, but selective binding of drugs to GPCRs is often limited.
  • Researchers developed specialized heavy-chain-only antibodies, known as 'nanobodies', that can selectively act as antagonists for the angiotensin II type I receptor, revealing unique mechanisms of how they block receptor activity.
  • The study demonstrates that these nanobodies can co-bind with small-molecule antagonists, providing a way to finely tune ligand selectivity, and highlights the potential of antibody fragments as advanced modulators for GPCRs in drug development.
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G protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue, and cellular level. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized.

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Antibodies are essential biological research tools and important therapeutic agents, but some exhibit non-specific binding to off-target proteins and other biomolecules. Such polyreactive antibodies compromise screening pipelines, lead to incorrect and irreproducible experimental results, and are generally intractable for clinical development. Here, we design a set of experiments using a diverse naïve synthetic camelid antibody fragment (nanobody) library to enable machine learning models to accurately assess polyreactivity from protein sequence (AUC > 0.

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Particulate methane monooxygenase (pMMO) is a copper-dependent integral membrane metalloenzyme that converts methane to methanol in methanotrophic bacteria. Studies of isolated pMMO have been hindered by loss of enzymatic activity upon its removal from the native membrane. To characterize pMMO in a membrane-like environment, we reconstituted pMMOs from () (Bath) and () 20Z into bicelles.

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The CopC proteins are periplasmic copper binding proteins believed to play a role in bacterial copper homeostasis. Previous studies have focused on CopCs that are part of seven-protein Cop or Pco systems involved in copper resistance. These canonical CopCs contain distinct Cu(I) and Cu(II) binding sites.

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